Delirium affects 60 to 80% of ventilated patients and is associated with worse clinical outcomes including death. Unfortunately, there are limited data regarding the prevalence and risk factors of delirium in critically ill burn patients. The objectives of this study were to evaluate the prevalence of delirium in ventilated burn patients, using validated instruments, and to identify its risk factors. Adult ventilated burn patients at two tertiary centers were prospectively evaluated for delirium using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) for 30 days or until intensive care unit discharge. Patients with neurologic injuries, severe dementia, and those not expected to survive >24 hours were excluded. Markov logistic regression was used to identify the risk factors of delirium, adjusting for clinically relevant covariates. The 82 ventilated burn patients had a median (interquartile range) age of 48 (38-62) years, Acute Physiology and Chronic Health Evaluation II scores 27 (21-30), and percent burns of 20 (732). Prevalence of delirium was 77% with a median duration of 3 (1-6) days. Exposure to benzodiazepines was an independent risk factor for the development of delirium (odds ratio: 6.8 [confidence interval: 3.1-15], P < .001), whereas exposure to both intravenous opiates (0.5 [0.4-0.6], P < .001) and methadone (0.7 [0.5-0.9], P = .02) was associated with a lower risk of delirium. In conclusion, delirium occurred at least once in approximately 80% of ventilated burn patients. Exposure to benzodiazepines was an independent risk factor for delirium, whereas opiates and methadone reduced the risk of developing delirium, possibly through reduction of pain in these patients.

Neurofeedback (NF) training has been employed as a therapeutic method in substance-dependence disorder over the last three decades. The purpose of the present study was to examine the effectiveness of this method on improvement of comorbid neuro-psychological syndromes in opioid-dependence disorder. Psychopathological and craving dimensions and brain activity signals of 20 opioid dependent patients were measured using Symptom Checklist-90-Revised (SCL-90-R), Heroin Craving Questionnaire (HCQ), and Quantitative Electroencephalography (QEEG). All the patients were undergoing pharmacotherapy. They were assigned to two groups that were matched based on SCL-90-R scores, education and age. The experimental group received 30 sessions of NF training in addition to their medicine. The control group received only the usual pharmacotherapy. The probable changes were monitored by reappraisal of all the patients after the treatment. We hypothesized that patients in the experimental group would show more reduction in their comorbid syndromes. The Multivariate Analysis of Covariance (MANCOVA) showed that the experimental group, in comparison with control group, showed significantly more improvement in all three outcome measures. In the SCL-90-R, improvement was noted with the hypochondriacs, obsession, interpersonal sensitivity, aggression, psychosis, and general symptomatic indexes. In the HCQ, improvement was found in the anticipation of positive outcome, desire to use substance, and total average score. Finally, the QEEG showed positive changes in frontal, central and parietal delta, frontal and central theta, parietal alpha and frontal and central Sensory Motor Rhythm (SMR) amplitudes. This study suggests that NF can be used as a therapeutic method to ameliorate abnormalities related to opioid-dependence disorders. The results emphasize the importance of neuropsychological interventions in treatment of substance-dependence disorders.

Office-based treatment of opioid dependence with buprenorphine has the potential to expand treatment capacity in the United States. However, nationally, little is known about the number, characteristics, and experiences of physicians certified to prescribe buprenorphine. Moreover, little is known about the impact of easing federal regulations on the number of patients a physician is allowed to treat concurrently. To address these questions, surveys of national samples of physicians certified to prescribe buprenorphine (2004-2008) were analyzed (N = 6,892). There has been a continual increase in the number of physicians certified to prescribe buprenorphine, increase in the mean number of patients treated by physicians, and decrease in patients turned away, coinciding temporally with easing of federal regulations. In addition, most physicians prescribed buprenorphine outside of traditional treatment settings. The U.S. experiment in expanding Schedule III-V medications for opioid dependence to physicians outside of formal substance abuse treatment facilities appears to have resulted in expanded capacity.

Methadone and buprenorphine are both efficacious treatments for opioid dependency, but they also have different pharmacological properties and clinical delivery methods that can affect their acceptability to patients. This study was intended to increase our knowledge of heroin-dependent individuals' perceptions of methadone vs. buprenorphine maintenance based on actual experiences with each. The study sample consists of heroin-dependent men at the Rikers Island jail in New York City who were voluntarily randomly assigned to methadone or buprenorphine maintenance in jail. Methadone patients were more likely to report feeling uncomfortable the first few days, having side/withdrawal effects during treatment, and being concerned about continued dependency on medication after release. In contrast, buprenorphine patients' main issue was the bitter taste. All of the buprenorphine patients stated that they would recommend the medication to others, with almost all preferring it to methadone. Ninety-three percent of buprenorphine vs. 44% of methadone patients intended to enroll in those respective treatments after release, with an added one-quarter of the methadone patients intending to enroll in buprenorphine instead. These results reinforce the importance of increasing access to buprenorphine treatment in the community for indigent heroin-dependent offenders.

Background: Significant gender differences in drug and alcohol use have been reported; however, little is known about gender differences in prescription opioid misuse and dependence. This study compared correlates, sources and predictors of prescription opioid non-medical use, as well as abuse or dependence among men and women in a nationally-representative sample. Methods: Participants were 55,279 (26,746 men, 28,533 women) non-institutionalized civilians aged 12 years and older who participated in the National Survey on Drug Use and Health. Results: Rates of lifetime and past-year non-medical use of prescription opiates were 13.6% and 5.1%, respectively. Significantly more men than women endorsed lifetime (15.9% vs. 11.2%) and past-year use (5.9% vs. 4.2%; ps < 0.0001). Among past-year users, 13.2% met criteria for current prescription opiate abuse or dependence, and this did not differ significantly by gender. Polysubstance use and treatment underutilization were common among both men and women, however significantly fewer women than men had received alcohol or drug abuse treatment (p = 0.001). Men were more likely than women to obtain prescription opioids for free from family or friends, and were more likely to purchase them from a dealer (ps < .01). Gender-specific predictors of use as compared to abuse/dependence were also observed. Conclusions: The findings highlight important differences between men and women using prescription opiates. The observed differences may help enhance the design of gender-sensitive surveillance, identification, prevention and treatment interventions.

Study objective: Ohio recently instituted an online prescription monitoring program, the Ohio Automated Rx Reporting System (OARRS), to monitor controlled substance prescriptions within Ohio. This study is undertaken to identify the influence of OARRS data on clinical management of emergency department (ED) patients with painful conditions. Methods: This prospective quasiexperimental study was conducted at the University of Toledo Medical Center Emergency Department during June to July 2008. Eligible participants included ED patients with painful conditions. Patients with acute injuries were excluded. After clinical evaluation, and again after presentation of OARRS data, providers answered a set of questions about anticipated pain prescription for the patient. Outcome measures included changes in opioid prescription and other potential factors that influenced opioid prescription. Results: Among 179 participants, OARRS data revealed high numbers of narcotics prescriptions filled in the most recent 12 months (median 7; range 0 to 128). Numerous providers prescribed narcotics for patients (median 3 per patient; range 0 to 40). Patients had filled narcotics prescriptions at different pharmacies (mean [SD] 3.5 [4.4]). Eighteen providers are represented in the study. Four providers treated 63% (N=114) of the patients in the study. After review of the OARRS data, providers changed the clinical management in 41% (N=74) of cases. In cases of altered management, the majority (61%; N=45) resulted in fewer or no opioid medications prescribed than originally planned, whereas 39% (N=29) resulted in more opioid medication than previously planned. Conclusion: The use of data from a statewide narcotic registry frequently altered prescribing behavior for management of ED patients with complaints of nontraumatic pain.

The sternoclavicular joint is an unusual site for bacterial infection In this case, we describe a 25-year-old man who presented to the emergency department with fever, chills, limited range of motion in the right upper limb along with complaints of severe pain and tenderness in the right upper chest wall and shoulder. He was admitted to the hospital for further evaluation This patient admitted to a history of injecting heroin use during the previous three months. The diagnosis of septic arthritis of the right sternoclavicular joint was confirmed by blood culture and MRI of the sternoclavicular joint. This case is, to the best of our knowledge, the 25th recorded staphylococcal septic sternoclavicular arthritis. He received appropriate intravenous antibiotic therapy and subsequently was discharged two weeks later with complete clinical and laboratory recovery.

Objective: How to best use urine drug test (UDT) results in the management of opioid pharmacotherapy has not been elucidated. The purpose of this study was to describe how the results of UDTs gathered from a group of chronic pain patients in a high-risk monitored opioid pharmacotherapy program apply to treatment outcome. Methods: Retrospective review of the medical records of 335 primary care patients on chronic opioids more than 22 months. Results: Patients with a UDT containing unprescribed opioids were more likely to demonstrate resolution of aberrant behavior (P = 0.02) and less likely to be discharged from treatment (P = 0.04). Patients with cocaine, alone or in combination, in the UDT were less likely to resolve aberrant behavior (P = 0.007 and 0.001), and were more likely to be electively or administratively discharged from treatment (P = 0.012 and 0.001). Discussion: In this group of high-risk pain patients on chronic opioids, information gained from UDT results can be used to predict treatment outcomes and inform appropriate interventions. Patients on chronic opioids who have a UDT positive for an illicit opioid or unprescribed opioids alone are more likely to respond to monitored opioid pharmacotherapy. Patients with a UDT positive for cocaine, alone or in combination, are less likely to resolve aberrant behavior within the structure of a monitored opioid pharmacotherapy program and are more likely to be discharged electively or administratively from the program without significant transition to addiction treatment. Further studies are needed to investigate which patient responded best to structured opioid pharmacotherapy programs and how to appropriately handle abnormal UDT results to improve the management and engagement in appropriate treatment for this population.

We have all encountered the following postanesthesia care unit dilemma a myriad of times. As the attending covering the postanesthesia care unit, the anesthesiologist will be confronted not infrequently with the following clinical scenario: "He needed 500 mu g fentanyl in the operating room for a toe amputation and has received 20 mg morphine, and he's still complaining of severe pain ... Do you think he may need more morphine?" Opiates do prevail as first-line therapy for moderate to severe surgical and chronic pain states. However, their use may actually confound the clinical picture postoperatively, because opiate exposure counterintuitively may actually trigger exaggerated pain sensation. When assessing a patient experiencing exaggerated postoperative or chronic pain, several questions should come to mind. First, is this patient experiencing tolerance or hyperalgesia induced by opiate therapy? Second, does the management differ for the two etiologies? Third, what underlying mechanisms, both at the neuroanatomic and molecular/chemical levels, underlie the two processes? Fourth, how does the recent literature on opiate-induced hyperalgesia influence previously accepted views of pre-emptive analgesia? Fifth, what treatment modalities exist for opiate-induced hyperalgesia? Most importantly, sixth, how can opiate-induced hyperalgesia be prevented? In this literature review, we aim to address these questions and to hopefully change the current perception and management of perioperative and chronic pain states with opiates.

Aims: Our study sought to assess the prevalence of and risk factors for opioid drug dependence among out-patients on long-term opioid therapy in a large health-care system. Methods: Using electronic health records, we identified out-patients receiving 4+ physician orders for opioid therapy in the past 12 months for non-cancer pain within a large US health-care system. We completed diagnostic interviews with 705 of these patients to identify opioid use disorders and assess risk factors. Results: Preliminary analyses suggested that current opioid dependence might be as high as 26% [95% confidence interval (CI) = 22.0-29.9] among the patients studied. Logistic regressions indicated that current dependence was associated with variables often in the medical record, including age < 65 [odds ratio (OR) = 2.33, P = 0.001], opioid abuse history (OR = 3.81, P < 0.001), high dependence severity (OR = 1.85, P = 0.001), major depression (OR = 1.29, P = 0.022) and psychotropic medication use (OR = 1.73, P = 0.006). Four variables combined (age, depression, psychotropic medications and pain impairment) predicted increased risk for current dependence, compared to those without these factors (OR = 8.01, P < 0.001). Knowing that the patient also had a history of severe dependence and opioid abuse increased this risk substantially (OR = 56.36, P < 0.001). Conclusion: Opioid misuse and dependence among prescription opioid patients in the United States may be higher than expected. A small number of factors, many documented in the medical record, predicted opioid dependence among the out-patients studied. These preliminary findings should be useful in future research efforts.

Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs

Background: There has been an increase in overdose deaths and emergency department visits (EDVs) involving use of prescription opioids, but the association between opioid prescribing and adverse outcomes is unclear. Methods: Data were obtained from administrative claim records from Arkansas Medicaid and HealthCore commercially insured enrollees, 18 years and older, who used prescription opioids for at least 90 continuous days within a 6-month period between 2000 and 2005 and had no cancer diagnoses. Regression analysis was used to examine risk factors for EDVs and alcohol- or drug-related encounters (ADEs) in the 12 months following 90 days or more of prescribed opioids. Results: Headache, back pain, and preexisting substance use disorders were significantly associated with EDVs and ADEs. Mental health disorders were associated with EDVs in HealthCore enrollees and with ADEs in both samples. Opioid dose per day was not consistently associated with EDVs but doubled the risk of ADEs at morphine-equivalent doses over 120 mg/d. Use of short-acting Drug Enforcement Agency Schedule II opioids was associated with EDVs compared with use of non Schedule II opioids alone (relative risk range, 1.09-1.74). Use of Schedule II long-acting opioids was strongly associated with ADEs (relative risk range, 1.64-4.00). Conclusions: Use of Schedule II opioids, headache, back pain, and substance use disorders are associated with EDVs and ADEs among adults prescribed opioids for 90 days or more. It may be possible to increase the safety of chronic opioid therapy by minimizing the prescription of Schedule II opioids in these higher-risk recipients.

Purpose. The implications of potential false-positive urine drug screen (UDS) results for patients receiving commonly prescribed medications were evaluated. Summary. A comprehensive literature review was conducted to identify false-positive UDSs associated with all clinic formulary medications, as well as common nonprescription medications. The references of each report describing a medication whose use was associated with false-positive UDS results were also reviewed. If a class effect was suspected, additional agents in the category were searched. A total of 25 reports of false-positive UDS results were identified. Categories of medications included antihistamines, antidepressants, antibiotics, analgesics, antipsychotics, and nonprescription agents. Reports of false-positive results were found for the following formulary and nonprescription medications: brompheniramine, bupropion, chlorpromazine, clomipramine, dextromethorphan, diphenhydramine, doxylamine, ibuprofen, naproxen, promethazine, quetiapine, quinolones (ofloxacin and gatifloxacin), ranitidine, sertraline, thioridazine, trazodone, venlafaxine, verapamil, and a nonprescription nasal inhaler. False-positive results for amphetamine and methamphetamine were the most commonly reported. False-positive results for methadone, opioids, phencyclidine, barbiturates, cannabinoids, and benzodiazepines were also reported in patients taking commonly used medications. The most commonly used tests to screen urine for drugs of abuse are immunoassays, even though false-positive results for drugs of abuse have been reported with a number of these rapid-screening products. Results from such tests should be confirmed using additional analytical methods, including gas chromatography-mass spectrometry. Conclusion. A number of routinely prescribed medications have been associated with triggering false-positive UDS results. Verification of the test results with a different screening test or additional analytical tests should be performed to avoid adverse consequences for the patients.

Introduction and Aims. The rate and correlates of infant death in those born to opioid-dependent women are unclear. This study aims to determine the infant mortality rate of infants born to women on a methadone program during pregnancy and to identify any modifiable risk factors. Design and Methods. A retrospective study of live births to all women in New South Wales, Australia during the period 1995-2002. Using record linkage four groups were compared: (i) live births to women on a methadone program during pregnancy who subsequently died during infancy; (ii) live births to women not on a methadone program who subsequently died during infancy; (iii) live births to women on a methadone program during pregnancy who did not die during infancy; and (iv) live births to women not on a methadone program who did not die during infancy. Results, Discussion and Conclusion. The infant mortality rate was higher among infants whose mothers were on methadone during pregnancy (24.3 per 1000 live born infants in group 1 and 4.0 per 1000 live born infants in group 2) compared with infants of all other mothers. The single main cause of death for all infants was Sudden Infant Death Syndrome. There was a higher rate of smoking among women on methadone. The findings suggest that methadone and non-methadone infant-mother pairs have different symptom profiles, diagnostic procedures and/or different patterns of access to care.

Introduction and Aims. Although clinical studies have noted that women with opioid use disorders use have high levels of mental and physical health disorders and are exposed to high levels of violence, it is not known whether this occurs at a level of severity that warrants hospital admission. Design and Methods. Administrative data from a jurisdictional methadone program were linked with hospital inpatient records from 1998 to 2002 to determine the main reasons for hospital admission for a cohort of women with a prior or ongoing history of methadone maintenance. Rates of hospital admissions by the cohort were compared with hospitalisations by all women without an opioid-related hospital diagnosis from 1998 to 2002. Results. After controlling for age, country of birth and marital status, women with a history of methadone maintenance had more frequent hospital admissions for the mental and behavioural disorders [relative risk (RR) 3.9 (95% confidence intervals (CI): 3.7, 4.0)], diseases of the skin and subcutaneous tissue [RR 2.1 (95% CI: 1.9, 2.3)]; injuries and poisonings [RR 2.0 (95% CI: 1.9, 2.1)] and infectious and parasitic diseases [RR 1.4 (95% CI: 1.2, 1.6)]. At a more detailed level of diagnostic specificity, the methadone cohort was admitted more often for hepatitis C, septicaemia and head injuries. Discussion and Conclusion. The elevated risk of hospital admission for a number of disorders suggests that women with a history of methadone maintenance experience these health events at a level of severity warranting hospital admission. Further contextual work is necessary to determine the effective preventive and management strategies.

Aims: To review and summarize existing prospective studies reporting on remission from dependence upon amphetamines, cannabis, cocaine or opioids. Methods: Systematic searches of the peer-reviewed literature were conducted to identify prospective studies reporting on remission from amphetamines, cannabis, cocaine or opioid dependence. Searches were limited to publication between 1990 and 2009. Reference lists of review articles and important studies were searched to identify additional studies. Remission was defined as no longer meeting diagnostic criteria for drug dependence or abstinence from drug use; follow-up periods of at least three years were investigated. The remission rate was estimated for each drug type, allowing pooling across studies with varying follow-up times. Results: There were few studies examining the course of psychostimulant dependence that met inclusion criteria (one for amphetamines and four for cocaine). There were ten studies of opioid and three for cannabis dependence. Definitions of remission varied and most did not clearly assess remission from dependence. Amphetamine dependence had the highest remission rate (0.4477; 95%CI 0.3991, 0.4945), followed by opioid (0.2235; 95%CI 0.2091, 0.2408) and cocaine dependence (0.1366; 95%CI 0.1244, 0.1498). Conservative estimates of remission rates followed the same pattern with cannabis dependence (0.1734; 95%CI 0.1430, 0.2078) followed by amphetamine (0.1637; 95%CI 0.1475, 0.1797), opioid (0.0917; 95%CI 0.0842, 0.0979) and cocaine dependence (0.0532; 95%CI 0.0502, 0.0597). Conclusions: The limited prospective evidence suggests that "remission" from dependence may occur relatively frequently but rates may differ across drugs. There is very little research on remission from drug dependence; definitions used are often imprecise and inconsistent across studies and there remains considerable uncertainty about the longitudinal course of dependence upon these most commonly used illicit drugs.

Objective: This study was designed to assess nonmedical prescription opioid use among a sample of opioid dependent participants. Methods: A cross-sectional survey was conducted with a convenience sample of patients hospitalized for medical management of opioid withdrawal. We collected data related to participant demographics, socioeconomic characteristics, the age of first opioid use, types of opioids preferred, and routes of administration. We also asked participants to describe how they first began using opioids and how their use progressed over time. Results: Among the 75 participants, the mean age was 32 years (SD: +/-11, range: 18-70 years), 49 (65%) were men, 58 (77%) considered themselves to be "white," 55 (74%) had a high school diploma or equivalent, and 39 (52%) were unemployed. All of these participants considered themselves to be "addicted." Thirty-one (41%) felt that their addiction began with "legitimate prescriptions," 24 (32%) with diverted prescription medications, and 20 (27%) with "street drugs" from illicit sources; however, 69 (92%) had reported purchasing opioids "off the street" at some point in time. Thirty-seven (49%) considered heroin to be their current preferred drug, and 43 (57%) had used drugs intravenously. Conclusions: We found that many treatment-seeking opioid-dependent patients first began using licit prescription drugs before obtaining opioids from illicit sources. Later, they purchased heroin, which they would come to prefer, because it was less expensive and more effective than prescription drugs.

We recently encountered a subject who died from an uncommon misuse of a fentanyl transdermal patch, chewing, followed by complications of aspiration of the patch. We report this case to alert medical examiners to the troubling trend of increased fentanyl patch abuse and its expanding range of misuses and associated morbidities. The decedent was a 28-year-old white male with a past medical history of prescription drug abuse who was pronounced dead in the emergency department shortly after arrival. An autopsy was completed and a tough but stretchy beige foreign body was identified lodged in a mainstem bronchus. Toxicological analysis of femoral blood showed methamphetamine, fentanyl and norfentanyl concentrations of 1456, 8.6 and 1.4 ng/mL, respectively. Individuals who abuse prescription medications often modify the route of administration of the drug from the intended method. As this case demonstrates, this choice can be fatal. The novel findings include a chewed patch, aspiration of a drug patch, and combination with an illicit drug at potentially lethal blood levels for both methamphetamine and fentanyl in a novice user.

Background: A key aim of supply-side drug law enforcement is to reduce drug use by increasing the retail price of drugs. Since most illicit drug users are polydrug users the effectiveness of this strategy depends on the extent to which drug users reduce their overall consumption of drugs. The literature shows that drug users do reduce their consumption of a drug when its price increases. However the extent of that decrease and the implications for the use of other drugs vary across studies. Methodology: A sample of 101 Australian methamphetamine users was surveyed using a behavioural economics approach. Participants were given a hypothetical fixed drug budget, presented with a range of drug price lists and asked how many units of each drug they would purchase. Methamphetamine and heroin prices were varied independently across trials. Results: While demand for both methamphetamine and heroin was found to be price elastic, elasticity estimates were influenced by the nature of participants' drug dependence. The group least responsive to changes in methamphetamine price were those dependent only on methamphetamine, while the group most responsive were dependent only on heroin. Similar findings emerged in relation to changes in heroin price. Cross-price elasticity analysis showed limited substitution into other drugs as the price of methamphetamine increased. In contrast, for heroin, there was significant substitution into pharmaceutical opioids and to a lesser extent, benzodiazepines and methamphetamine. However, for the most part, the decreases in methamphetamine or heroin consumption outweighed any substitution into other drugs. Conclusion: The reduction in overall drug consumption and expenditure in response to price increases in heroin and methamphetamine observed in this sample lend support to supply-side enforcement strategies that aim to increase retail drug price. Notably, this analysis highlights the importance of accounting for the nature of users' drug dependence in estimating price responsiveness.

This document reports the consensus of an interdisciplinary panel of research and clinical experts charged with reviewing the use of opioids for chronic noncancer pain (CNCP) and formulating guidelines for future research. Prescribing opioids for chronic noncancer pain has recently escalated in the United States. Contrasting with increasing opioid use are: 1) The lack of evidence supporting long-term effectiveness; 2) Escalating misuse of prescription opioids including abuse and diversion; and 3) Uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events (ADEs) including endocrine dysfunction, immunosuppression and infectious disease, opioid-induced hyperalgesia and xerostomia, overdose, falls and fractures, and psychosocial complications. Chief among the limitations of current evidence are: 1) Sparse evidence on long-term opioid effectiveness in chronic pain patients due to the short-term time frame of clinical trials; 2) Insufficiently comprehensive outcome assessment; and 3) Incomplete identification and quantification of ADEs. The panel called for a strategic interdisciplinary approach to the problem domain in which basic scientists and clinicians cooperate to resolve urgent issues and generate a comprehensive evidence base. It offered 4 recommendations in 3 areas: 1) A research strategy for studying the effectiveness of long-term opioid pharmacotherapy; 2) Improvements in evidence-generation methodology; and 3) Potential research topics for generating new evidence. Perspective: Prescribing opioids for CNCP has outpaced the growth of scientific evidence bearing on the benefits and harms of these interventions. The need for a strong evidence base is urgent. This guideline offers a strategic approach to creating a comprehensive evidence base to guide safe and effective management of CNCP.

Between April 2007 and March 2009 in the BEACH (Bettering the Evaluation and Care of Health) program, drug abuse was managed 770 times, at a rate of 0.4 per 100 encounters, suggesting it is managed by general practitioners about 436 000 times per year nationally. This article focuses on illicit drugs such as heroin and marijuana, and includes substances such as glue. Alcohol, tobacco and medicines are not included.

This study investigates recent (one-month) and lifetime prevalence of suicide attempts, and factors associated with one-month suicide attempts among heroin users (n = 488) seeking treatment at a methadone maintenance programme in Taiwan. Data were collected by structured interview on demographics, use of heroin and other substances, criminal convictions, depression, social networks, and history of suicide attempt (lifetime suicide attempt, and suicide attempt and suicide ideation in the previous month). Prevalence of recent (one-month) suicide attempt was 10.9% and lifetime prevalence was 17.8%. The finding that so many heroin users had made a suicide attempt in the very recent past is both disturbing and little researched. Recent suicidal attempts were associated with severity of heroin dependence, needle sharing, higher educational level, increased levels of depression, and number of stressful life events. It is suggested that methadone maintenance programmes should routinely screen at intake for previous suicidal behaviour and especially for recent suicidal attempts.

Purpose: Based on preclinical and clinical abuse liability assessments, fentanyl and other potent mu opioid agonists (e.g., hydromorphone and morphine) should be the most misused opioids if accessibility in the real world were not an issue. Since the latter is seldom true, we postulated that there would be a significant mismatch between actual and predicted rates of misuse. Methods: We recruited 1818 prescription-opioid dependent patients entering drug treatment programs to complete an anonymous survey, covering drug use and health related issues. Results: Hydrocodone and oxycodone products were the drugs of choice in 75% of patients, whereas potent pc opioid agonists (fentanyl, hydromorphone, and morphine), with the greatest predicted abuse potential, were very rarely chosen (<5% each). Most unexpectedly, the rank order of the actual drug of choice and the preferred drug in an ideal world were highly correlated. The reason most commonly given for the failure to endorse fentanyl, for example, as an actual or preferred drug, was fear of toxicity and overdose. We found few differences in drug use patterns between a subset of high-risk, impaired health care professionals (N = 196), and all other patients other than source of drug (forged prescriptions and doctors more common and dealers much less common in the HC sample). Conclusions: These results indicate that it should not be assumed - particularly for new drug formulations that a high potential for abuse will result in actual abuse; and, most importantly, that the hesitancy to use potent opioids because of fears of abuse may be misguided.

This study describes the prevalence of erectile dysfunction (ED) among 57 men using illicit opioids who presented to a primary care program for buprenorphine therapy. Participants' mean age was 40 years and 34% reported ED. Low total testosterone was detected in 17% of those reporting ED, but total testosterone was not significantly associated with ED. Examining multiple comorbidities and laboratory parameters, only older age was significantly associated with ED (r = .27, P .05). ED is highly prevalent among men abusing opioids, but low total testosterone is rarely the cause.

The purpose of this study was to examine the prevalence and risk factors for lifetime nonmedical use of sedative-hypnotics and opiates among a sample of rural and urban women with recent partner violence victimization (n = 756). Nearly one third of the sample (32.8%) reported ever using illicit sedative-hypnotics or opiates. Nonmedical use of sedative-hypnotics and opiates was significantly associated with lifetime cumulative exposure to interpersonal victimization, rural Appalachian residency, past-year use of other substances and other substance-related problems, and lifetime unmet health care needs. Findings have implications for substance abuse prevention and treatment and victim advocacy programs.

The relationship between pain and prescription opioid abuse is poorly understood. Determining whether a patient is seeking additional opioid medications in order to alleviate pain or to abuse the drugs can be difficult. The present study was designed to evaluate two variables that may influence the abuse liability of opioids: drug use history and the presence or absence of experimentally induced pain. Eighteen healthy participants completed this outpatient study. One group was abusing prescription opioids (N = 9) and one group had used prescription opioids medically but did not abuse them (N = 9). All participants completed twelve sessions during which the effects of orally delivered oxycodone (0, 15, 30 mg/70 kg, PO) were examined. One dose was tested per day under double-blind conditions and sessions were separated by at least 48 h. During the first "sample" session each week, participants were given $10 and the dose that was available later that week. During the second "choice" session, participants could self-administer either money or the previously sampled dose. Six sessions involved repeated hand immersions in cold water (4 degrees C) and six sessions involved immersions in warm water (37 degrees C). Most of the positive subjective effects of oxycodone were similar between the groups, but oxycodone self-administration significantly differed between groups. Non-abusers self-administered active doses of oxycodone only when they were in pain while abusers self-administered oxycodone regardless of the pain condition. These data suggest that an assessment of the reinforcing effects of opioids may be a sensitive method for differentiating opioid abusers from non-abusers.

The aim is to model treatment pathways and outcomes of opiate users at intake and at 1- and 3-year follow-up and to assess the implications of these for treatment policy. Opiate users entering a new treatment episode were recruited. Tree diagrams were used to map treatment relapse and re-entry. A within subjects repeated measures analyses of variance was conducted on each of the outcomes. The effect of being in treatment at 1-year on the 3-year outcomes was measured controlling for the value of the outcome variable at intake. A total of 404 opiate users were recruited. Follow-up interview rates were 88.4% at 3-years. Three years after intake 15% were drug free, 70% were in treatment and 15% were not in treatment and were using illegal drugs. Analysis revealed that there were no differences between the three outcome groups at intake. Those who were not in treatment and using at 3-years had displayed little improvement at 1-year and those who were not in treatment and not using at 3-years had displayed improvements in physical and mental health outcomes at 1-year. Regardless of treatment modality, treatment policy needs to reflect, support and encourage individuals during the treatment relapse cycle.

Individuals on methadone maintenance for the treatment of addiction (MM) are demonstrated to be hyperalgesic to cold-pressor pain in comparison to matched controls and ex-opioid addicts, a finding described as clinical evidence of opioid-induced hyperalgesia (OIH). Interestingly, opioids induce hyperalgesia via many of the same neuro-inflammatory and central sensitization processes that occur with the development of neuropathic pain. Evaluated in this study was the efficacy of a key pharmacotherapy for neuropathic pain, gabapentin (GPN), to reverse OIH in MM patients. Utilizing a clinical trial design and double blind conditions, changes in cold-pressor pain threshold and tolerance following a 5-week trial of GPN (titrated to 2400 mg/day) were evaluated at peak and trough methadone plasma levels in a well-characterized MM sample. Drug abstinence was encouraged via an escalating payment schedule, and compliance monitored via pill counts and GPN plasma levels; entered into the analyses were only those subjects compliant and abstinent throughout the study (approximately 45%). Utilizing change scores from baseline, significant improvements in cold-pressor pain threshold and pain tolerance were observed at both peak and trough methadone levels (p < 0.05). Notably, drop-out rates due to medication side effects were low (2%) and the medication was well-tolerated. These results support that GPN, as prescribed for the treatment of neuropathic pain, is effective in decreasing OIH in patients who are abstinent and stable in methadone treatment.

Background: Drug dependence is associated with both attentional biases to drug-related cues and inhibitory control deficits. Although acute stress is known to increase craving, it is not known whether this effect is mediated via changes in attentional bias and inhibitory control. Objectives: To examine the effect of a mild stressor on inhibitory control, attentional bias and craving in current opiate users (methadone maintained), ex-users (currently abstinent) and non-users (healthy controls). Method: Forty-eight participants (16 in each group) were exposed to both stress and non-stress conditions, after which inhibitory control and attentional bias was assessed using a Go-No-go and dot probe task respectively. Subjective ratings of stress levels and drug craving were repeatedly monitored. Results: Current opiate users had significantly higher cravings ratings than both other groups at all times, and their craving tended to increase following the stress task. Current users had a greater attentional bias towards drug-related stimuli than the ex-users. Interestingly, ex-users showed a bias away from drug-related stimuli in the stress condition and this correlated positively with their length of abstinence. On the Go/No-go task, all groups had fewer false alarms in the stress condition. Conclusions: These results indicate that successful treatment is associated with a bias away from drugs, and that this bias may be protective against the effects of stress.

Objective To investigate the effect of opiate substitution treatment at the beginning and end of treatment and according to duration of treatment. Design: Prospective cohort study. Setting UK General Practice Research Database Participants Primary care patients with a diagnosis of substance misuse prescribed methadone or buprenorphine during 1990-2005. 5577 patients with 267 003 prescriptions for opiate substitution treatment followed-up (17 732 years) until one year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice. Main outcome measures: Mortality rates and rate ratios comparing periods in and out of treatment adjusted for sex, age, calendar year, and comorbidity; standardised mortality ratios comparing opiate users' mortality with general population mortality rates. Results Crude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100 person years off treatment; standardised mortality ratios were 5.3 (95% confidence interval 4.0 to 6.8) on treatment and 10.9 (9.0 to 13.1) off treatment. Men using opiates had approximately twice the risk of death of women (morality rate ratio 2.0, 1.4 to 2.9). In the first two weeks of opiate substitution treatment the crude mortality rate was 1.7 per 100 person years: 3.1 (1.5 to 6.6) times higher (after adjustment for sex, age group, calendar period, and comorbidity) than the rate during the rest of time on treatment. The crude mortality rate was 4.8 per 100 person years in weeks 1-2 after treatment stopped, 4.3 in weeks 3-4, and 0.95 during the rest of time off treatment: 9 (5.4 to 14.9), 8 (4.7 to 13.7), and 1.9 (1.3 to 2.8) times higher than the baseline risk of mortality during treatment. Opiate substitution treatment has a greater than 85% chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months. Conclusions: Clinicians and patients should be aware of the increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment. Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality.

Offenders with a history of opioid dependence are a particularly difficult group to treat. A large proportion of offenders typically relapse shortly after release from prison, commit drug-related crimes, and then are arrested and eventually re-incarcerated. Previous research demonstrated that oral naltrexone was effective in reducing opioid use and preventing recidivism among offenders under federal supervision. The 111 opioid-dependent offenders in this study were under various levels of supervision that included county and federal probation/parole, a treatment court, an alternative disposition program, and an intermediate punishment program. Subjects were randomly assigned to receive 6 months of either 300 mg per week of oral naltrexone plus standard psychosocial treatment as usual (n = 56) or standard psychosocial treatment as usual (TAU) without naltrexone (n = 55). While the TAU subjects who remained in treatment used more opioids than the naltrexone subjects who remained, the high dropout rate for both groups made it difficult to assess the effectiveness of naltrexone. The study provides limited support for the use of oral naltrexone for offenders who are not closely monitored by the criminal justice system.

Copyright 2010, American Academy of Psychiatrists in Alcoholism and Addictions

Laboratory testing of oral fluid for drugs of abuse continues to expand in the workplace, legal, treatment, and health settings. In this study, we assessed recently developed homogeneous Roche DAT screening assays for amphetamines, cocaine metabolite [benzoylecgonine (BZE)], methamphetamines, and opiates in oral fluid. Precision and accuracy were assessed using control samples at ±25% of cutoff. Sensitivity, specificity, and agreement compared to liquid chromatography-tandem mass spectrometry (LC-MS-MS) was assessed by analysis of oral fluid specimens collected from 994 subjects enrolled in a drug treatment or probation and parole drug-testing program. An additional 180 research specimens from Kroll Laboratories were analyzed for amphetamine and methamphetamine. Screening cutoff concentrations (ng/mL) were as follows: amphetamines, 40; cocaine metabolite, 3; methamphetamines, 40; and opiates, 10. LC-MS-MS analyses were performed with the following cutoff concentrations (ng/mL): amphetamine, 40; BZE, 2.0; methamphetamine, 40; and codeine or morphine, 10. The percent coefficient of variation ranged from 3.4% to 7.3%. Sensitivity and specificity of the Roche DAT assays compared to LC-MS-MS were > 94%, and agreement was > 96% for the four assays. The performance of the Roche DAT assays suggests these new homogeneous screening assays will be an attractive alternative to existing more labor-intensive enzyme immunoassays.

Aims: Although illicit drug purity is a widely discussed health risk, research explaining its geographic variation within a country is rare. This study examines whether proximity to the US-Mexico border, the United States' primary drug import portal, is associated with geographic variation in US methamphetamine, heroin and cocaine purity. Design Distances (proximity) between the US-Mexico border and locations of methamphetamine, cocaine and heroin seizures/acquisitions (n = 239 070) recorded in STRIDE (System to Retrieve Information from Drug Evidence) were calculated for the period of 1990-2004. The association of drug purity with these distances and other variables, including time and seizure/acquisition size, was examined using hierarchical multivariate linear modeling (HMLM). Setting: Coterminous United States. Findings: Methamphetamine, cocaine and heroin purity generally decreased with distance from the US-Mexico border. Heroin purity, however, after initially declining with distance, turned upwards-a U-shaped association. During 2000-04, methamphetamine purity also had a U-shaped association with distance. For each of the three drugs, temporal changes in the purity of small acquisitions (< 10 g) were typically more dynamic in areas closer to the US-Mexico border. Conclusions: Geographic variance in methamphetamine, cocaine and heroin purity throughout the coterminous United States was associated with US-Mexico border proximity. The U-shaped associations between border-distance and purity for heroin and methamphetamine may be due to imports of those drugs via the eastern United States and southeast Canada, respectively. That said, areas closer to the US-Mexico border generally had relatively high illicit drug purity, as well as more dynamic change in the purity of small ('retail level') drug amounts.

Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs

The demographic and toxicological characteristics of deliberate (SUI, n = 50) and accidental (ACC, n = 927) fatal heroin overdose cases were examined. SUI cases were more likely to be female, had lower body mass indices, were more likely to be enrolled in treatment and less likely to have hepatic pathology. The median blood morphine concentration of SUI cases was significantly higher than that of ACC cases (0.70 vs. 0.40 mg/L, p < 0.001). Blood morphine concentrations of > 1 mg/L were seen among 38.0% of SUI cases compared to 13.9% of ACC cases. Being a member of the SUI group remained a significant independent predictor of higher morphine concentrations after controlling for the effects of potential confounders (p < 0.001), other significant predictors being the absence of alcohol (p < 0.001), the presence of methadone (p < 0.05), and the presence of cocaine (p < 0.05). The current data are consistent with the view that suicide forms a small, but distinct, category of heroin overdose cases, rather than overdose being a parasuicidal phenomenon per se.

Copyright 2010, Wiley-Blackwell

De Maeyer J; Vanderplasschen W; Broekaert E. Quality of life among opiate-dependent individuals: A review of the literature. (review). International Journal of Drug Policy 21(5): 364-380, 2010. (118 refs.)

Quality of life (QoL) has become an important outcome indicator in health care evaluation. A clear distinction has to be made between QoL - focussing on individuals' subjective satisfaction with life as a whole and different life domains - and health-related QoL (HRQoL), which refers to the absence of pathology. As opiate dependence is the primary drug of most persons entering treatment and as the attention for QoL in addiction research is growing, this review of the literature intends to summarise and differentiate the available information on QoL in opiate-dependent individuals. A comprehensive literature review was conducted, including database searches in Web of Science, Pubmed and Cochrane Database of Systematic Reviews. Articles were eligible for review if they assessed QoL or HRQoL of opiate-dependent individuals, used a QoL or HRQoL instrument and reported at least one specific outcome on QoL or HRQol. In total, 38 articles have been selected. The review showed that various instruments (n = 15) were used to measure QoL, mostly HRQoL instruments. Opiate-dependent individuals report low (HR)QoL compared with the general population and people with various medical illnesses. Generally, participation in substitution treatment had a positive effect on individuals' (HR)QoL, but long-term effects remain unclear. Psychological problems, older age and excessive alcohol use seem to be related with lower (HR)QoL scores. The assessment of QoL in research on opiate dependence is still in its infancy. Still, the chronic nature of drug use problems creates the necessity to look at outcomes beyond the direct consequences of drug dependence and based on clients' needs. HRQoL, with its unilateral focus on the functional status of clients, does not give information on clients' own experiences about the goodness of life, and is as a consequence unsuitable for measuring QoL. Future research starting from a subjective, multidimensional approach of the concept of QoL is required.

Objective: To examine prevalence of and associations between herpes simplex virus type 2 (HSV-2) infection and HIV infection among never-injecting heroin and cocaine drug users (NIDUs) in New York City. Methods: Subjects were recruited from patients entering the Beth Israel drug detoxification program. Informed consent was obtained, a structured questionnaire including demographics, drug use history, and sexual risk behavior was administered, and a blood sample was collected for HIV and HSV-2 antibody testing. Results: A total of 1418 subjects who had never (lifetime) injected drugs (NIDUs) were recruited between July 2005 through June 2009. Subjects were primarily male (76%), and black (67%) or Hispanic (25%), reported recent crack cocaine use (74%), and had a mean age of 42 years. Eleven percent of males reported male-with-male sexual (MSM) behavior. The prevalence of both viruses was high: for HSV-2, 61% among the total sample, 50% among non-MSM males, 85% among females, and 72% among MSM; for HIV, 16% among the total sample, 12% among non-MSM males, 20% among females, and 46% among MSM. HSV-2 was associated with HIV (OR = 3.2, 95% CI: 2.3-4.5; PR = 2.7, 95% CI: 2.0-3.7). Analyses by gender and age groups indicated different patterns in mono-and coinfection for the 2 viruses. Discussion: HSV-2 and HIV rates among these NIDUs are comparable with rates in sub-Saharan Africa. Additional prevention programs, tailored to gender and age groups, are urgently needed. New platforms for providing services to NIDUs are also needed.

Background: The field of heroin use disorder intervention has been in transition in South Africa since the outbreak of the heroin epidemic. Yet despite growing evidence of an association between heroin users' use of supplementary intervention services and intervention outcomes, heroin use disorder intervention programmes in South Africa generally fail to meet international research-based intervention standards. Methods: Semi-structured interviews with ten heroin use disorder specialists were conducted and the interviews were subjected to content analysis. Results and Discussion: In terms of theory and practice, findings of the study suggest that the field of heroin use disorder intervention in South Africa remains fragmented and transitional. Specifically, limited strategic public health care polices that address the syndromes' complexities have been implemented within the South Africa context. Conclusions: Although many interventions and procedures have begun to be integrated routinely into heroin use disorder clinical practice within the South African context, comorbidity factors, such as psychiatric illness and HIV/AIDS, need to be more cogently addressed. Pragmatic and evidence-based public health care policies designed to reduce the harmful consequences associated with heroin use still needs to be implemented in the South African context.

Drawing on concepts from Foucault and Agamben, we maintain that the lives of daily heroin users provide a prime illustration of bare life in the zone of indistinction that is contemporary Detroit. First, we consider the case of Detroit as a stigmatized and racially segregated city, with concrete consequences for its residents. We then present evidence from in-depth ethnographic and economic interviews to illustrate the various spaces of confinementthat of addiction, that of economic marginality, and that of gender occupied by these men and women, as well as the indeterminacy of their daily lives, captured through their descriptions of daily routines and interactions. We examine their expressions of worth as expressed in economic, emotional and moral terms. Finally, we draw connections between the sustained marginality of these individuals, as a contemporary category of homo sacer, and the policies and powers that both despise and depend upon them. Heroin, we contend, helps to fill and numb this social void, making bare life bearable, but also cementing one's marginality into semi-permanence.

Objective: To study physician and patient perceptions of moderate-to-severe chronic pain and its management with oral opioids. Methods: Two separate surveys were developed and administered to one of two respective study groups: patients and physicians. All study participants recruited from a pool of individuals who had previously agreed to participate in market research. Survey questions addressed the impact of various factors (e. g., quality of life indicators, potential for opioid addiction, side-effects) on pain management decision making, patient satisfaction and compliance. Responses for the first 500 patients and 275 physicians to respond were assessed using descriptive statistics. Results: On average, patients were 53 years of age, white (89%), and female (71%). The majority of patients (80%) had been taking oral opioids longer than 6 months. Physicians reported that 45% of their patients received schedule II opioids, with 27% having severe chronic pain. Patients indicated the most common activities interfered with by chronic pain were exercising (76% of patients), working outside the home (67%), and job responsibilities (60%). When developing a treatment approach physicians considered patients' sleeping (91%), walking (86%), maintaining an independent lifestyle (84%), and job responsibilities (83%). Patients and physicians both rated the ability to relieve pain and the duration of relief as the most important factors when considering opioid therapy. The majority (63%) of patients reported experiencing opioid side effects. When physicians discontinued opioids due to side effects, the most frequent reason was nausea (78%) for immediate-release opioids, and constipation (64%) for extended-release formulations. Conclusion: The ability to relieve pain and the duration of that pain relief are the most important factors for both patients and physicians when selecting an opioid. A high percentage of patients surveyed experienced side effects related to their treatment, which may impact adherence and overall treatment effectiveness. Study results should be assessed within study limitations including responder and selection biases, physicians responded about their patients, who were not the same patients surveyed, and the fact that the survey instruments were not formally validated. Further research is warranted to address these limitations.

Buprenorphine is a partial mu opioid receptor agonist with clinical efficacy as a pharmacotherapy for opioid dependence. A sublingual combination formulation was developed containing buprenorphine and naloxone with the intent of decreasing abuse liability in opioid-dependent individuals. However, the addition of naloxone may not limit abuse potential of this medication when taken by individuals without opioid physical dependence. The present study investigated the effects of buprenorphine alone and in combination with naloxone administered intramuscularly and sublingually to non-dependent opioid abusers. In a within-subject crossover design, non-dependent opioid-experienced volunteers (N = 8) were administered acute doses of buprenorphine (4, 8, and 16 mg) and buprenorphine/naloxone (4/1, 8/2, and 16/4 mg) via both intramuscular and sublingual routes, intramuscular hydromorphone (2 and 4 mg as an opioid agonist control), and placebo, for a total of 15 drug conditions. Laboratory sessions were conducted twice per week using a double-blind, double-dummy design. Buprenorphine and buprenorphine/naloxone engendered effects similar to hydromorphone. Intramuscular administration produced a greater magnitude of effects compared to the sublingual route at the intermediate dose of buprenorphine and at both the low and high doses of the buprenorphine/naloxone combination. The addition of naloxone did not significantly alter the effects of buprenorphine. These results suggest that buprenorphine and buprenorphine/naloxone have similar abuse potential in non-dependent opioid abusers, and that the addition of naloxone at these doses and in this dose ratio confers no evident advantage for decreasing the abuse potential of intramuscular or sublingual buprenorphine in this population.

Opioid dependence is largely an undertreated medical condition in the United States. The introduction of buprenorphine has created the potential to expand access to and use of opioid agonist treatment in generalist settings. Physicians, however, often have limited training and experience providing this type of care. Some physicians believe having a mentoring relationship with an experienced provider during their initial introduction to the use of buprenorphine would ease implementation. Our goal was to describe the development, implementation, resources, and evaluation of the Physician Clinical Support System-Buprenorphine (PCSS-B), a federally funded program to improve access to and quality of treatment with buprenorphine. We provide a description of the PCSS-B, a national network of 88 trained physician mentors with expertise in buprenorphine treatment and skills in clinical education. We provide information regarding the use the PCSS-B core services including telephone, email and in-person support, a website, clinical guidances, a warmline and outreach to primary care and specialty organizations. Between July 2005 and July 2009, 67 mentors and 4 clinical experts reported providing mentoring services to 632 participants in 48 states, Washington DC and Puerto Rico. A total of 1,455 contacts were provided through email (45%), telephone (34%) and in-person visits (20%). Seventy-six percent of contacts addressed a clinical issue. Eighteen percent of contacts addressed a logistical issue. The number of contacts per participant ranged from 1-125. Between August 2005 and April 2009 there were 72,822 visits to the PCSS-B website with 179,678 pages viewed. Seven guidances were downloaded more than 1000 times. The warmline averaged more than 100 calls per month. The PCSS-B model provides support for a mentorship program to assist non-specialty physicians in the provision of buprenorphine and may serve as a model for dissemination of other types of care.

Despite a lower prevalence of opioid dependence among females, drug-related problems and risk factors such as prostitution have a negative effect for women in treatment. This study was conducted with the purpose of analyzing gender differences in the German trial on heroin-assisted treatment (HAT), which compared HAT with methadone maintenance treatment (MMT). Significant baseline gender differences were found, with females showing a greater extent of mental distress. Differences in retention and outcome were significant for male patients, but no differences between treatment options were found for female patients. Ongoing prostitution was found to influence drug use outcomes. Other outcome criteria may need to be stressed when assessing the effect of HAT for women.

Background: To improve the delivery of health services for chronic medical conditions in our methadone clinic, we added an onsite health screening and brief health counseling to the treatment plans for patients receiving methadone maintenance treatment (MMT) at the Atlanta Veterans Affairs Medical Center. We then conducted a follow-up retrospective chart review to assess whether this intervention improved health outcome for those patients. Methods: We reviewed the charts of 102 patients who received treatment at Atlanta Veterans Affairs Medical Center methadone clinic between 2002 and 2008. We sought to determine whether our increased health education and screening intervention were associated with (1) improved drug addiction outcome (as measured by comparing percentage of opiate and cocaine positive drug screens from admission with most recent). (2) Basic health screening (as measured by the patient's compliance with primary care physician appointments and current smoking status). (3) Management of co-occurring medical conditions (as measured by levels of low-density lipoprotein cholesterol, hemoglobin A1c, and systolic blood pressure). (4) Presence of QT interval corrected (QTc) prolongation (difference in QTc between baseline and most recent electrokardiogram). Results: Illicit drug use (opiate and cocaine) markedly decreased in patients overall. The effect was more robust for those successfully "retained" (n = 55, P < 0.0001) in treatment, compared with those who "dropped out" (n = 40, P = 0.05) of treatment. Compliance with primary care physician appointments was high (82% and 88% before and after the onsite intervention, respectively) for retained patients. Low-density lipoprotein cholesterol level was within normal range for all patients. A1c improved by 40% after the onsite intervention as reflected by the decreased percentage of patients with A1c >7% from before to after the intervention (90% vs 50%, P =0.05). However, the prevalence of uncontrolled hypertension did not significantly improve after the onsite intervention (38% vs 28%, P = 0.34). As might be expected with MMT, the prevalence of QTc prolongation actually increased from 399 (+/- 92) to 439 (+/- 22) milliseconds after the onsite intervention (P = 0.003). Conclusions: Our retrospective study supports the previous literature that methadone maintenance therapy is effective in reducing illicit drug use. Although patients with history of heroin dependence and in MMT are at increased risk for chronic medical conditions, such as hepatitis C and diabetes, there are minimal federal guidelines for medical care, except than a physical examination on admission, and basic screening for some infectious diseases, eg, HIV and hepatitis C for those patients. Our study demonstrated the need for and potential benefit of enhancing the delivery of health promotion services for chronic medical conditions in methadone maintained patients. Improving management of hepatitis C, diabetes, hypertension, and other related conditions, in this high risk, difficult-to-treat, and underserved population may reduce their morbidity and premature mortality.

Introduction: To examine hospitalizations in a cohort of 224 patients who presented with non-fatal heroin overdose to an ED. Methods: A record linkage study, using the morbidity, mental health and mortality databases in the Data Linkage Unit of the Department of Health, Western Australia. The main outcome measures were hospital separations 5 years before and after entry into the cohort. Results: Before entry into the cohort, 199 (89%) patients had an admission to mental health services. These 199 had a combined total of 1367 separations, most commonly for a mental health condition, injury or poisoning. Women had more than twice the relative risk (RR) of men for all separations (RR 2.35, 95% confidence interval [CI] 1.96-2.82, P < 0.001) and for injury and poisoning separations (RR 2.04, 95% CI 1.56-2.66, P < 0.001). The highest concentrations of separations occurred within 1 year before and 1 year after entry into the cohort. There were 12 (5.4%, 95% CI 2.9-9.4%) deaths, most commonly from overdose. Conclusion: Non-fatal heroin overdose ED presentations are associated with a cluster of hospitalizations around that episode, likely to be related to heroin availability. Presentation to hospital by heroin users represents an opportunity to counsel less risky behaviour.

Background: Several types of medications have been used for stabilizing heroin users: Methadone, Buprenorphine and levo-alpha-acetyl-methadol (LAAM.) The present review focuses on the prescription of heroin to heroin-dependent individuals. Objectives: To compare heroin maintenance to methadone or other substitution treatments for opioid dependence regarding: efficacy and acceptability, retaining patients in treatment, reducing the use of illicit substances, and improving health and social functioning. Search strategy; A review of the Cochrane Central Register of Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to 2008), EMBASE (1980 to 2005) and CINAHL until 2005 (on OVID) was conducted. Personal communication with researchers in the field of heroin prescription identified other ongoing trials. Selection criteria; Randomised controlled trials of heroin maintenance treatment (alone or combined with methadone) were compared with any other pharmacological treatment for heroin-dependent individuals. Data collection and analysis: Two reviewers independently assessed trial quality and extracted data. Main results: Eight studies involving 2007 patients were included. Results show marginal significance in favour of heroin for remaining in treatment until the end of the study (8 studies, N= 2007, RR= 1.23, 95% CI= 0.96-1.57; heterogeneity P < 0.01). Adverse events are significantly more frequent in the heroin group. Heroin plus methadone prescription for maintenance treatment in adult chronic opioid users who failed previous methadone treatment attempts decreases the use of other illicit substances (3 Studies, N= 1289, RR= 0.63, 95% CI= 0.49, 0.81, heterogeneity P= 0.21), and reduces the risk of being incarcerated (2 studies, N= 1103, RR= 0.64, 95% CI= 0.51-0.79, heterogeneity P= 0.31). In addition, we also found a marginally significant protective effect of heroin prescription plus methadone for the use of street heroin (3 studies, N= 1512, RR= 0.70, 95% CI= 0.49-1.00, heterogeneity P < 0.01) and for criminal activity (4 studies, N= 1377, RR= 0.80, 95% CI= 0.61-1.04, heterogeneity P= 0.31). There was not enough power to detect statistically significant results for the risk of death (5 studies, N= 1817, RR= 0.77, 95% CI= 0.32-1.87, heterogeneity P= 0.79). Authors' conclusions: The available evidence suggests a small added value of heroin prescribed alongside flexible doses of methadone for long- term, treatment refractory opioid users, considering a decrease in the use of street heroin and other illicit substances, and in the probability of being imprisoned; and an increase in retention in treatment. Due to the higher rate of serious adverse events, heroin prescription should remain a treatment of last resort for people who are currently or have in the past failed maintenance treatment.

A review of methadone-related issues and the approach to heroin addicted patients is presented with the aim to clarify what is practiced by the establishment of anti-craving treatment and what is expected within a history of addiction. A series of clinical situations occurring throughout pregnancy to early child development are described, and the etiological hypothesis discussed. Moreover, some methodological considerations are described in order to better understand some ambiguity about the effectiveness and harmlessness of methadone treatment, particularly with regard to neonatal opiate withdrawal. Limitations to the outcome of pregnancies in heroin addicted women seems to be due to misconceptions about methadone toxicity and neonatal damage, which may lead to the mishandling of methadone as a therapeutic modality, especially with regard to maintenance at effective dosages.

Objective: To assess the prevalence of nonmedical prescription opioid use (NMPOU) in the Canadian general adult population in the context of rising overall prescription opioid (PO) consumption and related problems in North America. Method: The prevalence of NMPOU was assessed as a multiitem construct in the Canadian Alcohol and Drug Use Monitoring Survey (CADUMS; n = 16 672), an ongoing cross-sectional monthly random digit dialing telephone survey representative of the general Canadian population, aged 15 years and older. CADUMS data were collected between April and December of 2008 with a response rate of 43.5%. Results: About 22% of CADUMS respondents reported PO use in the last year, while 0.5% reported NMPOU during the same time frame. PO use was significantly higher among women than among men, and highest in the group aged 25 to 54 years. NMPOU was similar among men and women, and highest in the group aged 15 to 24 years. Conclusions: CADUMS data indicate an extremely low rate of NMPOU, especially given the levels of overall PO use, other PO-use related problems, and NMPOU levels estimated in the general US population where NMPOU has been assessed to be 10 times higher than in Canada. NMPOU survey item construction and response rates appear to strongly influence and potentially compromise NMPOU survey data. Existing NMPOU data and survey methods need to be validated for this important indicator in Canada, where increasing PO use and problem levels have been recognized as a significant and rising public health problem.

Background: North America is the region with the world's highest prescription opioid (PO) use. Nonmedical use of prescription opioids and PO-related morbidity and mortality have strongly increased in the US in recent years. It is assumed that similar trends are occurring in Canada, but there is less empirical evidence to support this. Treatment demand for problematic PO use is an important indicator of PO-related morbidity. Methods: Levels and changes related to the caseload of PO-related treatment admissions were assessed using system-level data from the Drug and Alcohol Treatment Information System (DATIS), the reporting system for publicly funded addiction treatment services in the province of Ontario (Canada) for the period April 2004-March 2009 (n = 500,217). In addition, basic socio-demographic and clinical characteristics of PO-related treatment admissions in the final year of study (n=10,125) were examined. Results: The number of PO-related treatment admissions in DATIS rose by 60%, and their prevalence in the total caseload increased from 9.4% to 15.7% in the study period. Three-quarters of PO-clients reported other problem substances: the most common co-occurring problem substance was cocaine/crack. The majority of PO-clients were <35 years of age, unemployed, and referred to treatment by others. Interpretation: Demand for treatment for problematic PO use has risen substantially in Ontario in the past five years in the wider context of substantially increased overall PO use and related harms in Canada. The interaction dynamics between these different indicators need to be systematically examined and monitored as the basis for evidence-based interventions.

Objectives. The objectives for presenting these medico-legal forensic case reports are the following: 1) detail three cases where chronic opioid analgesic therapy (COAT) was alleged to cause iatrogenic addiction and/or re-addiction; 2) detail the plaintiff's and defendant's medical experts' opinions on these allegations; and 3) through analyzing these cases, develop some recommendations for future prevention of such allegations during COAT. Methods. Case Reports. Results. Medico-legal issues surrounding the allegation of iatrogenic addiction were identified in each case. Conclusions. Before starting COAT, physicians should obtain and document patient informed consent for the risk of addiction/re-addiction with COAT treatment. Patients with a history of addictions pre-COAT should be placed on adherence monitoring immediately on beginning COAT.

Background: Opioid dependence is an increasing problem among adolescents and young adults, but in contrast to the standard in the adult population, adoption of pharmacotherapies has been slow. Extended-release naltrexone (XR-NTX) is a promising treatment that has been receiving increasing interest for adult opioid dependence. Clinical chart abstractions were performed on a convenience sample of 16 serial adolescent and young adult cases (mean age 18.5 years) treated for opioid dependence with XR-NTX who attended at least one out-patient clinical follow-up visit. Case descriptions: Of these 16 cases, 10 of 16 (63%) were retained in treatment for at least 4 months and nine of 16 (56%) had a 'good' outcome defined as having substantially decreased opioid use, improvement in at least one psychosocial domain and no new problems due to substance use. Conclusions: These descriptive results suggest that XR-NTX in the treatment of adolescents and young adults with opioid dependence is well tolerated over a period of 4 months and feasible in a community-based treatment setting, and associated with good outcomes in a preliminary, small non-controlled case-series. This probably reflects an overall trend towards greater adoption of medication treatments for this population.

Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs

Freckelton SCI. Mental Illness, sentencing and execution: The disturbing death of an Englishman in China. (editorial). Psychiatry, Psychology and Law 17(3): 333-344, 2010. (36 refs.)

Execution is one of the indispensable means of education. Deng Xiaoping (1904-1997) Come little rabbit Come to me, Come little rabbit Let it be, Come little rabbit Come and pray, Only one people, Only one world, Only one God. Akmal Shaikh (1956-2009) [image omitted]The tragic saga of the execution of a British citizen, Akmal Shaikh, in Urumqi in northwest China in December 2009 highlights the risks of mental illnesses such as bipolar disorders and delusional disorders being discounted or inadequately taken into account in terms of their impact upon criminal responsibility and criminal culpability. The strong evidence is that Shaikh was seriously delusional and incapable of exercising reasoned judgements in his own best interests when he was found with heroin in his possession upon entering China. Yet he was not permitted to be examined by mental health professionals and was executed, after appeals, including to the Supreme People's Court of China, failed. The Shaikh case is a warning to all legal systems that a range of mental illnesses can generate symptoms causing those with them to have little insight but which, when properly evaluated, may be exculpatory or at least significantly mitigatory.

Background: Addiction to opioids, or opioid dependence, encompasses the biopsychosocial dysfunction seen in illicit heroin injectors, as well as aberrant behaviours in patients prescribed opioids for chronic nonmalignant pain. Objective: To outline the management of opioid dependence using opioid pharmacotherapy as part of a comprehensive chronic illness management strategy. Discussion: The same principles and skills general practitioners employ in chronic illness management underpin the care of patients with opioid dependence. Opioid pharmacotherapy, with the substitution medications methadone and buprenorphine, is an effective management of opioid dependence. Training and regulatory requirements for prescribing opioid pharmacotherapies vary between jurisdictions, but this treatment should be within the scope of most Australian GPs.

Objective: To investigate morbidity related to misuse of over-the-counter (OTC) codeine-ibuprofen analgesics. Design and setting: Prospective case series collected from Victorian hospital-based addiction medicine specialists between May 2005 and December 2008. Main outcome measures: Morbidity associated with codeine-ibuprofen misuse. Results: Twenty-seven patients with serious morbidity were included, mainly with gastrointestinal haemorrhage and opioid dependence. The patients were taking mean daily doses of 435-602 mg of codeine phosphate and 6800-9400 mg ibuprofen. Most patients had no previous history of substance use disorder. The main treatment was opioid substitution treatment with buprenorphine-naloxone or methadone. Conclusions: Although codeine can be considered a relatively weak opioid analgesic, it is nevertheless addictive, and the significant morbidity and specific patient characteristics associated with overuse of codeine-ibuprofen analgesics support further awareness, investigation and monitoring of OTC codeine-ibuprofen analgesic use.

Background: Anabolic-androgenic steroids (AAS) have long been used by body-builders seeking to increase muscle size, strength and beauty. AAS are sometimes used together with narcotic agents and are thought to serve as a gateway to narcotic substance use, but this theory has not yet been substantiated clinically or sociologically. Methods: Mandatory interviews were carried out with individuals (n = 56) suspected of infringement of the narcotic laws in Sweden with confiscated and/or confirmed use of AAS. Data were collected over 12 months. Results: Seventy-three percent of subjects with confirmed use of AAS were also using narcotic substances. The use of AAS was preceded by the use of narcotic agents in 55% of subjects. Only one-fifth of the subjects in the study had used AAS before using narcotic agents. Conclusion: Co-use of AAS and narcotics agents is frequent among young people taken into custody for criminal activity and investigated by the police in Sweden. The study does not lend support to the hypothesis that AAS are commonly a gateway drug to narcotic use.

Copyright 2010, Elsevier Science

Gingras M; Laberge MH; Lefebvre M. Evaluation of the usefulness of an oxycodone immunoassay in combination with a traditional opiate immunoassay for the screening of opiates in urine. Journal of Analytical Toxicology 34(2): 78-83, 2010. (7 refs.)

Oxycodone is a semisynthetic opioid analgesic largely prescribed for post-operative and chronic pain management. The introduction of a slow release formulation of oxycodone has led to its frequent abuse and to an increase in emergency cases related to oxycodone overdose. Until recently, oxycodone testing has been confined to gas chromatography-mass spectrometry (GC-MS) analysis because the widely used automated opiate immunoassays poorly react to this compound. We investigated the utility of a new oxycodone immunoassay as a screening procedure to eliminate inappropriate GC-MS testing of negative urine specimens. We analyzed 96 urine specimens using GC-MS and two immunoassays, CEDIA(r) opiates and DRI(r) oxycodone assays from Microgenics, on a Hitachi 917 analyzer. The GC-MS allowed us to detect codeine, hydrocodone, hydromorphone, morphine, oxycodone, and oxymorphone following enzymatic hydrolysis and derivation by acetylation. The combination of the two immunoassays gave the best performance (98% sensitivity and specificity) when considering a positive result from GC-MS for any of the opiates. Considering positive GC-MS results for oxycodone or oxymorphone only, the oxycodone immunoassay resulted in two false-positives and one false-negative (50 ng/mL cutoff). Using these immunoassays for screening before GC-MS analysis provides a reduced opiate GC-MS workload without compromising quality.

Background: In opioid maintenance treatment (OMT) there are documented treatment differences both between countries and between OMT programmes. Some of these differences have been associated with staff attitudes. The aim of this study was to 1) assess if there were differences in staff attitudes within a national OMT programme, and 2) investigate the associations of staff attitudes with treatment organisation, clinical practices and outcomes. Methods: This study was a cross-sectional multicentre study. Norwegian OMT staff (n = 140) were invited to participate in this study in 2007 using an instrument measuring attitudes towards OMT. The OMT programme comprised 14 regional centres. Data describing treatment organisation, clinical practices and patient outcomes in these centres were extracted from the annual OMT programme assessment 2007. Centres were divided into three groups based upon mean attitudinal scores and labelled; "rehabilitation-oriented", "harm reduction-oriented" and "intermediate" centres. Results: All invited staff (n = 140) participated. Staff attitudes differed between the centres. "Rehabilitation-oriented" centres had smaller caseloads, more frequent urine drug screening and increased case management (interdisciplinary meetings). In addition these centres had less drug use and more social rehabilitation among their patients in terms of long-term living arrangements, unemployment, and social security benefits as main income. "Intermediate" centres had the lowest treatment termination rate. Conclusions: This study identified marked variations in staff attitudes between the regional centres within a national OMT programme. These variations were associated with measurable differences in caseload, intensity of case management and patient outcomes.

Fear of engendering addiction is frequently reported as both a provider and a patient barrier to effective pain management. In this study, a clinical scenario ascertained nursing staff members' usual practice in addressing addiction fears for patients with concerns about the addictive potential of pain medication. One hundred forty-five Veterans Health Administration nursing staff members from eight ambulatory care sites were queried to identify variables associated with proclivity to address patient fears about addiction risks in a population where pain is prevalent and the risk for substance abuse is high. Regarding addressing addiction concerns, 66% of nursing staff were very likely, 16% somewhat likely, 9% unsure, 6% somewhat unlikely, and 2% very unlikely to take action. Health technicians were less likely to address addiction concerns than registered or licensed vocational nurses (odds ratio [OR] 0.116; p=.004). Nursing staff with more years' experience (OR 1.070; p=.005) and higher levels of self-efficacy/confidence (OR 1.380; p=.001) were more likely to engage in discussions related to addiction risks. Targeted efforts to improve pain management activities should focus on retaining experienced nursing staff in initial assessment positions and improving the skills and confidence of less experienced and less skilled staff.

Background: Buprenorphine is a mixed-activity, partial p-opioid agonist. Its lipid solubility makes it well suited for transdermal administration. Objective: This study assessed the efficacy and safety profile of a 7-day buprenorphine transdermal system (BIDS) in adult (age >18 years) patients with moderate to severe chronic low back pain previously treated with tablet daily of an opioid analgesic. Methods: This was a randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phase. After a 2- to 7-day washout of previous opioid therapy, eligible patients were randomized to receive BTDS 10 mu g/h or matching placebo patches. The dose was titrated weekly using 10- and 20-mu g/h patches (maximum, 40 mu g/h) based on efficacy and tolerability. After 4 weeks, patients crossed over to the alternative treatment for another 4 weeks. Patients who completed the double-blind study were eligible to enter the 6-month open-label phase. Rescue analgesia was provided as acetaminophen 325 mg to be taken as 1 or 2 tablets every 4 to 6 hours as needed. The primary outcome assessments were daily pain intensity, measured on a 100-mm visual analog scale (VAS), from no pain to excruciating pain, and a 5-point ordinal scale, from 0 = none to 4 = excruciating. Secondary outcome assessments included the Pain and Sleep Questionnaire (100-mm VAS, from never to always), Pain Disability Index (ordinal scale, from 0 = no disability to 11 = total disability), Quebec Back Pain Disability Scale (categorical scale, from 0 = no difficulty to 5 = unable to do), and the 36-item Short Form Health Survey (SF-36). Patients and investigators assessed overall treatment effectiveness at the end of each phase; they assessed treatment preference at the end of double-blind treatment. After implementation of a precautionary amendment, the QTc interval was measured 3 to 4 days after randomization and after any dose adjustment. All assessments performed during the double-blind phase were also performed every 2 months during the open-label extension. Adverse events were collected by non-directed questioning throughout the study. Results: Of 78 randomized patients, 52 (66.7%) completed at least 2 consecutive weeks of treatment in each study phase without major protocol violations (per-protocol [PP] population: 32 women, 20 men; mean [SD] age, 51.3 [11.4] years; mean weight, 85.5 [19.5] kg; 94% white, 4% black, 2% other). The mean (SD) dose of study medication during the last week of treatment was 29.8 (12.1) mu g/h for BTDS and 32.9 (10.7) mu g/h for placebo (P = NS). During the last week of treatment, BTDS was associated with significantly lower mean (SD) pain intensity scores compared with placebo on both the VAS (45.3 [21.3] vs 53.1 [24.3] mm, respectively; P = 0.022) and the 5-point ordinal scale (1.9 [0.7] vs 2.2 [0.8]; P = 0.044). The overall Pain and Sleep score was significantly lower with BTDS than with placebo (177.6 [125.5] vs 232.9 [131.9]; P = 0.027). There were no treatment differences on the Pain Disability Index, Quebec Back Pain Disability Scale, or SF-36; however, BTDS was associated with significant improvements compared with placebo on 2 individual Quebec Back Pain Disability Scale items (get out of bed: P = 0.042; sit in a chair for several hours: P = 0.022). Of the 48 patients/physicians in the PP population who rated the effectiveness of treatment, 64.6% of patients (n = 31) rated BTDS moderately or highly effective, as did 62.5% of investigators (n = 30). Among the 50 patients in the PP population who answered the preference question, 66.0% of patients (n = 33) preferred the phase in which they received BTDS and 24.0% (n = 12) preferred the phase in which they received placebo (P = 0.001), with the remainder having no preference; among investigators, 60.0% (n = 30) and 28.0% (n = 14) preferred the BTDS and placebo phases, respectively (P = 0.008), with the remainder having no preference. The mean placebo-adjusted change from baseline in the QTc interval ranged from -0.8 to +3.8 milliseconds (P = NS). BIDS treatment was associated with a significantly higher frequency of nausea (P < 0.001), dizziness (P < 0.001), vomiting (P = 0.008), somnolence (P = 0.020), and dry mouth (P = 0.003), but not constipation. Of the 49. patients completing 8 weeks of double-blind treatment, 40(81.6%) entered the 6-month, open-label extension study and 27 completed it. Improvements in pain scores achieved during the double-blind phase were maintained in these patients. Conclusions: In the 8-week, double-blind portion of this study, BIDS 10 to 40 mu g/h was effective compared with placebo in the management of chronic, moderate to severe low back pain in patients 11 had previously received opioids. The improvements in pain scores were sustained throughout the 6-month, open-label extension.

METHODS: Data were collected from students (N = 7058) participating in 2 randomized controlled trials of a school-based substance abuse prevention program implemented across the United States. Students provided substance use and demographic information on a self-reported survey. Data for the physical disrepair of schools were collected from individual rater observations of each school environment. We hypothesized that school disrepair would be positively associated with substance use controlling for individual characteristics and a socioeconomic status proxy. Multilevel mixed modeling was used to test the hypothesized association and accounted for students nested within schools. RESULTS: Findings indicated that students attending an alternative HS with greater school disrepair were more likely to report the use of marijuana and other illicit drugs (ie, cocaine, heroin). Students attending regular HS with greater school disrepair were less likely to report smoking cigarettes. CONCLUSIONS: Differences in findings between regualr HS and alternative HS students are discussed, and implications for substance use prevention programming are offered. Students attending alternative HS with greater school disrepair may require more substance abuse prevention programming, particularly to prevent illicit substance use.

Global health and conflict studies share key linkages that have important research and policy implications but for which data are currently lacking. This analytical review examines the ongoing conflict in Afghanistan, using it as a basis to develop a conceptual framework that integrates security and public health concepts. The analysis draws on recent peer-reviewed and gray literature to assess the interrelationship among 3 variable clusters and their impact on the emergence of the HIV epidemic in Afghanistan. The evidence suggests that there is a complex indirect relationship linking illicit opium trade, the ongoing insurgency, and forced and spontaneous migration to the emergence of an injection drug use-driven HIV epidemic in Afghanistan. These findings demonstrate a clear need for an integrated cross-disciplinary and regional approach to the emerging threat of HIV/AIDS in Afghanistan, to inform more balanced and effective policy making in this and other regions of strategic global import.

Introduction: Research suggests that methadone maintenance treatment (MMT) effectively reduces opiate dependence and related health and social problems. However, few studies have examined its effectiveness among the elderly. This study examined a monthly MMT regime for elderly opium addicts attending the National Addictions Management Service, Singapore. Materials and Methods: This study used a cross-sectional design and comprised 40 patients attending the addiction service and 40 caregivers who monitored methadone consumption (mostly patients' sons and daughters). Participants completed a semi-structured interview comprising measures of opiate craving and withdrawal, physical and psychological health. Objective measures were urine drug screens and blood tests. Results: Participants who averaged 74.8 years old had been using opium for around 44 years and had been in MMT for an average of 35 months. The maintenance dose of methadone was 9.2 mg/day. At interview, no opiate usage (other than methadone) was detected in urine screens; however, clinical records indicated that 6 had tested positive during the previous 6 months of MMT. No major withdrawal symptoms, side effects, or incidents of diversion were reported. Quality-of-life scores were in the normal range and satisfaction with the treatment regime was expressed by caregivers. Conclusion: Whilst MMT is the predominant pharmacotherapy for opiate dependence for users of all ages elsewhere, our study group constitutes a unique population that differs markedly from younger opiate users who will eventually grow old. In Singapore, MMT appears to be an effective treatment for stable, elderly opium-dependent patients where families are fully engaged in the treatment regime.

Background and aims: There are growing concerns regarding visual outcome of infants exposed to opiates (including substitute methadone) and/or benzodiazepines in utero. We describe the combined ophthalmology and visual electrophysiology findings in 20 infants and children who had been exposed to substitute methadone and other drugs of misuse in utero. Methods: This was a descriptive case series of 20 patients, all of whom had been referred to a paediatric visual electrophysiology service because of concerns regarding visual function, and all of whom had been exposed to methadone in utero. All children underwent a full ophthalmic and orthoptic examination as well as visual electrophysiology testing deemed appropriate on an individual basis. A review was undertaken of paediatric case notes and of maternal antenatal urine toxicology. Results: Ophthalmic abnormalities included reduced acuity (95%), nystagmus (70%), delayed visual maturation (50%), strabismus (30%), refractive errors (30%), and cerebral visual impairment (25%). Visual electrophysiology was abnormal in 60%. A quarter of the children had associated neurodevelopmental abnormalities. The majority of children with nystagmus (79%) had been treated for neonatal abstinence syndrome (NAS). Conclusion: Infants born to drug-misusing mothers prescribed methadone in pregnancy are at risk of a range of visual problems, the underlying causes of which are not clear. Those infants with NAS severe enough to receive pharmaceutical treatment may be at particular risk of developing nystagmus. The inclusion of visual electrophysiology in comprehensive visual assessment of children exposed to substance misuse in utero may help clarify the underlying causes by differentiating abnormalities of retinal and cortical origin.

Many persons seeking opiate treatment present with complex clinical challenges, which may be exacerbated by alcohol misuse. This report details secondary data analyses aggregating treatment-seeking samples across 10 National Institute on Drug Abuse (NIDA) Clinical Trials Network treatment trials to examine alcohol-related characteristics of opiate-primary (OP) clients and compare broad pretreatment characteristics of those with and without an alcohol use disorder (AUD). Analysis of this aggregate OP client sample (n = 1,396) indicated that 38% had comorbid AUD and that a history of alcohol treatment episodes and recent alcohol problems were common. Further, comparisons of OP clients with and without AUD revealed the former were more likely to have had a history of pervasive difficulties in psychosocial functioning. Findings suggest the need for detection of and intervention for alcohol misuse at the outset of opiate treatment and support for the practice of availing medical, psychological, case management, and other support services.

Objectives: The purpose of this study was to examine both medical and nonmedical use of benzodiazepines among a community-based cohort of prescription opioid users. Methods: A total of 221 prescription opioid users from 2 rural Appalachian counties were recruited to participate in an interviewer-administered survey assessing sociodemographic characteristics, medical (source was valid prescription) and nonmedical (source other than prescription, such as dealer, friend, or family member) prescription drug use, illicit substance use, psychiatric disorders, and pain. Results: Almost all of the participants (92.8%) reported lifetime benzodiazepine use and two thirds were current users. Only 29.3% of the current users had a legitimate prescription for a benzodiazepine. Current users were significantly more likely than nonusers to report nonmedical use of a variety of prescription opioids and other illicit drugs. The major source of benzodiazepines was a dealer. Conclusions: A high rate of nonmedical benzodiazepine use was observed in this sample of prescription opioid users. Physicians should, therefore, be aware of the potential for nonmedical use of benzodiazepines. Implications for treatment and future research are discussed.

This article focuses on one residential therapeutic community for the treatment of heroin and opiate addiction in contemporary China. It discusses 2 case vignettes and shows that although addictions are extremely difficult to treat, there are small successes being reached in China's southwest. Residential treatment communities follow mobile global practices that link Western models of 12-step Narcotics Anonymous, self-healing, to other Chinese practices like Maoist "speak bitterness." In China it is in the drug aid theaters where Sunlight-International traveled to do three things: (a) stave off the American drug market, (b) reduce drug trafficking across national borders, and (c) address the psychosocial problems associated with global drug trafficking and consumption. Through the process of unraveling the on-the-ground practices of public health international humanitarian nongovernmental organizations and some of their therapeutic models, we begin to see new alliances formed across the globe around drug treatment and care that point toward important results.

The aim of this study was to investigate temperament, hopelessness (a measure of suicide risk), and health perception in heroin addicts. The study involved the administration of the TEMPS-A Rome, the Beck Hopelessness Scale (BHS), the MINI Neuropsychiatric Interview, and the Multidimensional Health Questionnaire. Participants were 100 heroin addicts who were matched by age and sex with 100 randomly selected non-users. Heroin addicts obtained higher scores on TEMPS-A Dys/Cyc/Anx temperament and on the irritable temperament. In the heroin addicts, anxiety, depression, preoccupation with health, health illness self-blame, health monitoring, and negative thinking about health were positively associated with hopelessness, dysthymic/anxious/cyclothymic temperament, and irritable temperament. Motivation to avoid unhealthiness, health assertiveness, health expectation optimism, and health satisfaction were negatively associated with hopelessness, dysthymic/anxious/cyclothymic temperament, and irritable temperament. More knowledge on health attitudes in heroin addicts may help in delivering a treatment plan for this selective population.

Chronic pain patients who show aberrant drug-related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain. The purpose of this study was to conduct a randomized trial in patients who were prescribed opioids for noncancer back pain and who showed risk potential for or demonstration of opioid misuse to see if close monitoring and cognitive behavioral substance misuse counseling could increase overall compliance with opioids. Forty-two patients meeting criteria for high-risk for opioid misuse were randomized to either standard control (High-Risk Control; N = 21) or experimental compliance treatment consisting of monthly urine screens, compliance checklists, and individual and group motivational counseling (High-Risk Experimental; N = 21). Twenty patients who met criteria indicating low potential for misuse were recruited to a low-risk control group (Low-Risk Control). Patients were followed for 6 months and completed pre- and post-study questionnaires and monthly electronic diaries. Outcomes consisted of the percent with a positive Drug Misuse Index (DMI), which was a composite score of self-reported drug misuse (Prescription Drug Use Questionnaire), physician-reported abuse behavior (Addiction Behavior Checklist), and abnormal urine toxicology results. Significant differences-were found between groups with 73.7% of the High-Risk Control patients demonstrating positive scores on the DMI compared with 26.3% from the High-Risk Experimental group and 25.0% from the Low-Risk Controls (p < 0.05). The results of this study demonstrate support for the benefits of a brief behavioral intervention in the management of opioid compliance among chronic back pain patient at high-risk for prescription opioid misuse.

Background: Neonatal abstinence syndrome (NAS) expression is widely variable among affected infants and the reasons for this variability are largely unknown; mechanisms that predispose infants to NAS expression are not understood. It has been postulated that the regulatory problems of prenatally drug exposed infants are manifested in dysfunctional vagal regulation of autonomic processes. The current study examines whether cardiac vagal tone, an indicator of parasympathetic neuroregulation, provides a marker for autonomic dysregulation subsequently expressed as NAS in prenatally opioid-exposed newborns. Methods: Heart period (HP) and cardiac vagal tone (V) were derived from electrocardiogram data collected from 64 methadone-exposed infants on postnatal days 1 and 3. The postpartum NAS course was assessed serially. Results: Infants with lower V on day 1 had significantly higher NAS symptomatology on day 3. Boys had more severe NAS symptoms than girls through the first 4 days of life and, among infants receiving pharmacologic treatment for NAS, boys required longer treatment course and hospitalizations. Greater poly-drug exposure, detected through toxicology screening throughout pregnancy, and cocaine use in particular, were associated with lower V and shorter HP (faster heart rate) in newborns. Multiple regression models accounted for 25-35% of the variance in NAS symptoms and duration of hospitalization in methadone-exposed infants. Significant predictors included infant sex, SSRI/SNRI use, and cigarette smoking. Conclusions: Results support the hypothesis of a biologic vulnerability of autonomic regulatory functioning in methadone-exposed infants and greater male infant vulnerability to maternal methadone use.

Cirrhosis due to chronic infection with hepatitis C virus remains by far the most common reason for liver transplantation in North America. Currently, parenteral use of street drugs is the most common means of acquiring hepatitis C. Methadone maintenance therapy is an accepted form of treatment for chronic opiate (eg, heroin) addiction and, not surprisingly, a significant proportion of methadone-treated patients have chronic hepatitis C. The feasibility of liver transplant candidacy in hepatitis patients who require methadone maintenance therapy is controversial, and some transplant centers require patients to withdraw from such therapy in order for the transplant process to move forward. Thus stable patients with end-stage cirrhosis who are receiving methadone maintenance are left in a most difficult situation: discontinue methadone and accept the side effects of withdrawal with the risk of recidivism to use of street opiates, an absolute contraindication for transplantation, or continue methadone therapy and risk exclusion from the transplant process. The issue of methadone replacement therapy in end-stage cirrhosis and the posttransplant literature on the subject are explored in this paper.

Unaided and abrupt cessation of opiate use without drug substitution and step-down, referred to as "cold turkey," is a common and difficult process for substance users, and is associated with several withdrawal symptoms and complications. This report presents a preliminary series of patients treated at an urban public hospital with acute perforation of peptic ulcers following abrupt cessation of long-term opiate use, a phenomenon that has not been previously described in the literature. Thirty-five patients with acute gastroduodenal perforation and a history of opiate addiction with a recent and abrupt cessation of opiate use were admitted between February 2004 and October 2008. This study evaluated the demographics, antecedent drug use, substance use characteristics, previous medical or surgical treatment of peptic ulcer disease, and surgical findings. The mean age was 32.3 years (range, 21-41 years) and the patients were overwhelmingly male (94%). The most frequent agent in single opiate users was opium (62.9%) followed by heroin (22.9%). The time interval between opiate cessation and perforation onset was 2-65 days (mean, 6.1 days). All patients underwent an immediate exploratory laparotomy, and the majority of perforations were found to be in the postpyloric area (94%) with mean size of 4.3 x 5.1 mm. Two patients (6%) had perforations in the lesser curvature of the stomach. All of the perforations occurred following sudden self-cessation without step-down or classic maintenance therapy, and this may prove the importance of supervised medical detoxification with special attention to gastroprotective agents such as antacid drugs.

The number of older adults needing substance abuse treatment is projected to rise significantly in the next few decades. This paper will focus on the epidemic of prescription use disorders in older adults. Particular vulnerabilities of older adults to addiction will be considered. Specifically, the prevalence and patterns of use of opioids, stimulants, and benzodiazepines will be explored, including the effects of these substances on morbidity and mortality. Treatment intervention strategies will be briefly discussed, and areas for future research are suggested.

Background: Patient satisfaction surveys, widely used in health care delivery systems, may provide useful data for improving patient retention and outcomes. Objectives: This study examined the relationship between methadone patients' treatment satisfaction at three months post-admission and their 3-month treatment outcomes and 12-month treatment retention. Methods: New methadone treatment admissions (N = 283) were assessed at 3 months post-admission for satisfaction with their counselors and programs. Correlations examined the relationship between 3-month satisfaction and Addiction Severity Index (ASI) scores. Regression analysis assessed the relationship between satisfaction and drug testing at 3 months and was used to predict whether participants were retained in treatment at 12 months. Results: Participants who were more satisfied with their counselors and programs had lower Drug and Legal ASI composite scores at 3 months. Participants who were more satisfied with their programs remained in treatment for at least 12 months. Conclusions: Treatment programs should consider administering the CEF to their patients at 3 months post-admission to identify patients with low satisfaction scores who may be at risk for prematurely leaving treatment. Scientific Significance: Measuring patient satisfaction during treatment may help programs meet patients' needs and improve retention.

Researchers have identified the association between the use of cocaine and sexual behavior as an important risk factor for HIV infection and have attempted to elucidate the nature of this association. Several lines of research have suggested that facilitation of sexual behavior during intoxication with cocaine may be because of the direct pharmacological effects of the drug (e.g., increase in sexual desire), whereas others have pointed to the importance of factors related to the context of drug use (e.g., opportunities for sexual behavior, expectations about the effects of the drug, social norms). The present study explored the perceived effects of cocaine and heroin on sexual behavior, as well as the social context of drug use as a function of drug type (cocaine vs. heroin), among 46 inner-city drug users who reported a history of regular use of both crack cocaine and heroin. Results indicated that compared to heroin, cocaine had deleterious effects on participants' perceived sexual desire and performance. Despite such deleterious effects on sexual behavior, cocaine was more frequently used with an intimate partner than heroin. Furthermore, participants did not differ in the extent to which they used the two drugs in other social contexts (e.g., with friends, family, or neighbors). These preliminary results suggest that the relationship between cocaine and sexual behavior, especially among long-term cocaine users, may be facilitated by opportunities for sex that exist in the context of cocaine use, rather than by the pharmacological effects of the drug.

Background: Iran is a significant consumer of opium, and, generally, of opioids, in the world. Addiction is one of the important issues of the 21st century and is an imperative issue in Iran. Longterm consumption of opioids affects homeostasis. Objective: To determine the effects of opium and heroin consumption on serum biochemical parameters. Methods: In a cross-sectional study, subjects who had consumed heroin (n = 35) or opium (n = 42) for more than two years and 35 nonaddict volunteers as the control group were compared in regard to various biochemical parameters such as fasting blood sugar (FBS), Na+, K+, Ca2+, blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG), cholesterol, creatinine, and total protein. Chromatography was used to confirm opioid consumption, and the concentration of biochemical parameters was determined by laboratory diagnostic tests on serum. Results: No significant differences were found in Na+, Ca2+, BUN, UA, TG, creatinine, and total protein concentrations among the three groups. FBS, K+, and UA levels were significantly lower in opium addicts compared to the control group. Serum Ca2+ concentration of heroin addicts showed a significant decrease compared to that of the control group. Both addict groups showed a significant decrease in serum cholesterol levels. Conclusion: Chronic use of opium and heroin can change serum FBS, K+, Ca2+, UA, and cholesterol. Scientific Significance: This study, one of few on the effects of opium on serum biochemical parameters in human subjects, has the potential to contribute to the investigation of new approaches for further basic studies.

Background: Opiate abuse has been linked to oxidative stress, through the separate evaluation of oxidants and antioxidants. Objectives: To determine prooxidant-antioxidant balance (PAB) in chronic heroin users in a single assay, easily applied in a clinical setting. Specifically, to examine whether PAB values correlate with the duration of abuse or with the presence of anti-HCV antibodies. Methods: Sixty-four chronic heroin users - 34 cases and 30 controls - participated in this study. PAB was determined by an Enzyme-linked immunosorbent assay (ELISA) method, developed by members of the study group. Results: In heroin users, oxidative balance was disrupted in favor of prooxidants. There was no correlation of PAB values with the duration of abuse or with the presence of anti-Hepatitis C virus (HCV) antibodies. Conclusions: Chronic heroin users can benefit from an antioxidant therapy, and the method currently presented can be used as an identification criterion.

Copyright 2010, Taylor & Francis

Kreek MJ. Overview and historical perspective of four papers presented on research related to the endogenous opioid system. (editorial). Drug and Alcohol Dependence 108(3, special issue): 195-199, 2010. (28 refs.)

Aims: Naltrexone is a competitive opioid antagonist that effectively blocks the action of heroin and other opioid agonists. Sustained-release naltrexone formulations are now available that provide long-acting opioid blockade. This study investigates the use of heroin and other opioids among opioid-dependent patients receiving treatment with long-acting naltrexone implants, their subjective experience of drug 'high' after opioid use, and factors associated with opioid use. Methods: Participants (n = 60) were opioid-dependent patients receiving treatment with naltrexone implants. Outcome data on substance use, drug 'high', depression and criminal activity were collected over a 6-month period. Blood samples were taken to monitor naltrexone plasma levels, and hair samples to verify self-reported opioid use. Findings: More than half [n = 34 or 56%; 95% confidence interval (CI) 44-68%)] the patients challenged the blockade with illicit opioids during the 6-month treatment period; 44% (n = 26; 95% CI 32-56%) were abstinent from opioids. Mean opioid use was reduced from 18 [standard deviation (SD)13] days during the month preceding treatment to 6 days (SD 11) after 6 months. Of the respondents questioned on opioid 'high' (n = 31), nine patients (30%; 95% CI 16-47%) reported partial drug 'high' following illicit opioid use, and three (12%; 95% CI 3-26%) reported full 'high'. Opioid use was associated with use of non-opioid drugs and criminal behaviour. Conclusions: Challenging naltrexone blockade with heroin on at least one occasion is common among sustained-release naltrexone patients, but only a minority of patients use opioids regularly. Challenges represent a warning sign for poor outcomes and often occur in the context of polydrug use and social adjustment problems.

Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs

Background: Naltrexone's usefulness in the treatment of opioid dependence stems from its ability to block the action of heroin and other opioids. However, many patients are ambivalent towards naltrexone and often drop out of treatment with orally administered naltrexone. Sustained release naltrexone seems promising in reducing opioid use, but the extent to which patients remain in treatment beyond the first dosage of naltrexone is not clear. Methods: Patients (n = 61) receving treatment with sustained release naltrexone implants were offered a second naltrexone implant after 6 months. Patients who remained in treatment were compared to those who did not, on drug use, mental health, and social problems before and during naltrexone implant treatment. Information was obtained on other treatments sought by patients who discontinued naltrexone. Blood samples were used to verify naltrexone release, and hair samples to confirm opioid intake. Results: Of the patients who received the first naltrexone implant, 51% (n = 31) remained in naltrexone implant treatment. Among those who discontinued treatment, 21% expressed a wish to reimplant but failed to attend for reimplantation and 28% declined reimplantation: 6 non-retained patients initiated maintenance or residential treatment. Remaining in naltrexone treatment was related to pre-study length of employment, illicit drug use, and concern for family problems. Higher levels of substance misuse and criminal activity during naltrexone treatment were negatively related to subsequent retention. Conclusion: Rates of retention among opioid-dependent patients receiving naltrexone implant treatment are encouraging and support this as a feasible long-term treatment option.

Background. With the growth in opioid therapy for the treatment of chronic pain, health care providers have focused their attention on avoiding over-use of opioid medications, specifically to avoid addiction, dependency, and other misuse. Qualitative and quantitative reviews of medication adherence, in contrast, focus primarily on why patients under-use or do not take their medications as prescribed and find nonadherence rates of approximately 25%. Objective. To identify the prevalence of under-use of opioid medications and the reasons and implications of under-use. Design. As part of a variety of structured assessments, subjects were asked detailed questions about how they used their opioid medication in their daily lives. Participants. One hundred ninety-one veterans who received an opioid prescription for any pain problem within the 12 months before the interview. Measures. We defined a patient who under-used his/her medication as one who took less than their prescribed dose of medication and reported that pain impaired their ability to engage in normal daily activities. Results. Under-use of opioids (20%) was more common than over-use (9%), consistent with research on medication adherence. Patients who under-used their opioids offered the same reasons for under-use that patients report for other medications. However, while under-users reported more pain than other opioid users they filled only slightly fewer opioid prescriptions. Communication problems between patients and providers about opioids were common. Conclusions. Improved communication between patients and providers and shared decision-making regarding opioid prescriptions may improve pain management and minimize the problems associated with over-prescription of opioids (i.e., diversion).

Introduction and Aims. Multiple substance use leads to greater levels of psycho-behavioural problems, unsafe sex, and therefore a high risk of contracting sexually transmitted diseases, and is also more difficult to treat. This study aims to determine pattern of lifetime multiple substance use among Chinese heroin users before entering methadone maintenance treatment clinic. Design and Methods. A survey to obtain retrospective longitudinal data on lifetime multiple substance use was conducted among 203 heroin users in two of the biggest methadone maintenance clinics in Kunming City, Yunnan province. Results. All participants used more than one substance in their lifetime. Most of them used four or more substance groups (range two to seven groups). The most common substance patterns in lifetime use were alcohol, tobacco, opiates and depressants. Approximately 80% of them had a history of simultaneous substance use (co-use). The most common combination of co-use pattern was heroin with depressant. Common reasons for co-use were to get high, to experiment, to sleep and to increase the potency of other drugs. Determinants of co-use were education, marital status and family relationship. Discussion and Conclusions. Multiple substance use is highly prevalent among Chinese heroin users. Depressants are the most common substances used in combination with heroin.

Introduction: The rates of cigarette smoking remain extremely high in active heroin users and methadone-maintained patients. It remains undetermined whether smoking status and motivation would be differentially affected by heroin and methadone administration. Methods: Heroin-dependent, methadone-maintained patients were recruited in the present studies. A battery of self-report questionnaires was used in the current study, in order to assess smoking status and motivations before first heroin use, during active heroin use and after Methadone Maintenance Treatment (MMT) admission. Results: An extremely high portion of participants started smoking before first heroin use. The highest level of cigarette smoking was found during the period of active heroin use, and cigarette consumption was reported to decrease after MMT admission. A wide range of smoking motivations were found before first heroin use. Moreover, "maintaining heroin pleasure" was the primary motivation for the increase in cigarette consumption during the period of active heroin use and 1 h after heroin administration, while "habitual smoking" was the primary smoking motivation before first heroin use and after MMT admission respectively. Conclusions: The present study first demonstrated that the prolonged rewarding effect of heroin following cigarette smoking may account for the increase of nicotine consumption found in the heroin-dependent patients. It appears that heroin and methadone differentially influenced smoking status and motivation among heroin-dependent, methadone-maintained patients.

Context: Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms. Objective: To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence. Design, Setting, and Participants A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants. Intervention: After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients. Main Outcome Measure: The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24. Results The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P=.04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (PCopyright 2010, American Medical Association

Background: Neonatal abstinence syndrome (NAS) occurs in more than 50% of infants exposed to intrauterine opiates. Maternal opiate dosing has been investigated with conflicting results. Aims: The aims of this study were to correlate maternal methadone dose and other risk factors with the development of NAS requiring pharmacological treatment by using easily accessible clinical parameters. Methods: Retrospective medical record review of data from 228 opioid dependent pregnant women who delivered 232 live-born infants. Logistic regression analysis was performed on maternal, perinatal and neonatal parameters to identify risk factors for NAS requiring treatment. A prediction model was developed and validated on a separate independent cohort of 188 infants. Results: Of the 232 infants, 172 (74%) infants were treated for NAS. The risk of withdrawal increased by 17% per 5 mg increment of the last maternal methadone dose. The risk was lower for younger gestational ages and for those delivered by Caesarean section compared to those delivered by normal vaginal delivery. Through predictive modeling, gestational age, mode of delivery and last methadone dose were established as risk factors for withdrawal. The model was validated by other statistical measures and its diagnostic performance confirmed on the separate independent cohort. Conclusions: Our data suggests that timing and mode of delivery as well as last maternal methadone dose are significant risk factors for the development of NAS requiring treatment. Based on these clinical parameters, risk stratification for perinatal management of pregnancies associated with opioid dependency and risk prediction for the neonate might now be possible.

Background: After prison release, offenders with heroin use problems are at high risk of relapse and overdose death. There is a particular need for treatments that can be initiated in prison and continued after release into the community. Methadone maintenance treatment has been shown to reduce heroin use, criminality and mortality. Naltrexone implant treatment has not previously been evaluated in prison settings. Methods: This study compares the effects of naltrexone implants and methadone treatment on heroin and other illicit drug use, and criminality among heroin-dependent inmates after release from prison. Results: Forty-six volunteers were randomly allocated to naltrexone implants or methadone before release. Intention-to-treat analyses showed reductions in both groups in frequency of use of heroin and benzodiazepines, as well as criminality, 6 months after prison release. Conclusions: Naltrexone implants may be a valuable treatment option in prison settings.

While long-term heroin addiction is associated with hypothalamus-pituitary-adrenal (HPA) axis dysregulation, few studies have used in vivo brain imaging to examine the impact on pituitary gland volume (PGV) or its relationship with substitution pharmacotherapy. We examined 28 heroin users stable on methadone or buprenorphine and 28 healthy controls. Heroin users exhibited larger PGVs than healthy controls, and this was particularly evident among the buprenorphine-treated group. These findings indicate that substitution pharmacotherapy may have differential effects on normalising HPA axis activity.

The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme that degrades the endogenous cannabinoid N-acylethanolamine (NAE) anandamide and the endogenous non-cannabinoid NAEs oleoylethanolamide and palmitoylethanolamide, blocks nicotine-induced excitation of ventral tegmental area (VTA) dopamine (DA) neurons and DA release in the shell of the nucleus accumbens (ShNAc), as well as nicotine-induced drug self-administration, conditioned place preference and relapse in rats. Here, we studied whether effects of FAAH inhibition on nicotine-induced changes in activity of VTA DA neurons were specific for nicotine or extended to two drugs of abuse acting through different mechanisms, cocaine and morphine. We also evaluated whether FAAH inhibition affects nicotine-, cocaine- or morphine-induced actions in the ShNAc. Experiments involved single-unit electrophysiological recordings from DA neurons in the VTA and medium spiny neurons in the ShNAc in anesthetized rats. We found that URB597 blocked effects of nicotine and cocaine in the ShNAc through activation of both surface cannabinoid CB1-receptors and alpha-type peroxisome proliferator-activated nuclear receptor. URB597 did not alter the effects of either cocaine or morphine on VTA DA neurons. These results show that the blockade of nicotine-induced excitation of VTA DA neurons, which we previously described, is selective for nicotine and indicate novel mechanisms recruited to regulate the effects of addicting drugs within the ShNAc of the brain reward system.

Endogenous opioids acting at mu-opioid receptors mediate many biological functions. Pharmacological intervention at these receptors has greatly aided in the treatment of acute and chronic pain, in addition to other uses. However, the development of tolerance and dependence has made it difficult to adequately prescribe these therapeutics. A common single nucleotide polymorphism (SNP), A118G, in the mu-opioid receptor gene can affect opioid function and, consequently, has been suggested to contribute to individual variability in pain management and drug addiction. Investigation into the role of A118G in human disease and treatment response has generated a large number of association studies across various disease states as well as physiological responses. However, characterizing the functional consequences of this SNP and establishing if it causes or contributes to disease phenotypes have been significant challenges. In this manuscript, we will review a number of association studies as well as investigations of the functional impact of this gene variant. In addition, we will describe a novel mouse model that was generated to recapitulate this SNP in mice. Evaluation of models that incorporate known human genetic variants into a tractable system, like the mouse, will facilitate the understanding of discrete contributions of SNPs to human disease.

The treatment of chronic pain, therapeutic opioid use and abuse, and the nonmedical use of prescription drugs have been topics of intense focus and debate. After the liberalization of laws governing opioid prescribing for the treatment of chronic non-cancer pain by state medical boards in the late 1990s, and with the introduction of new pain management standards implemented by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in 2000, opioids, in general, and the most potent forms of opioids including Schedule II drugs, in particular, have dramatically increased. Despite the escalating use and abuse of therapeutic opioids, nearly 15 to 20 years later the scientific evidence for the effectiveness of opioids for chronic non-cancer pain remains unclear. Concerns continue regarding efficacy; problematic physiologic effects such as hyperalgesia, hypogonadism and sexual dysfunction; and adverse side effects especially the potential for misuse and abuse and the increase in opioid-related deaths. Americans, constituting only 4.6% of the world's population, have been consuming 80% of the global opioid supply, and 99% of the global hydrocodone supply, as well as two-thirds of the world's illegal drugs. Retail sales of commonly used opioid medications (including methadone, oxycodone, fentanyl base, hydromorphone, hydrocodone, morphine, meperidine, and codeine) have increased from a total of 50.7 million grams in 1997 to 126.5 million grams in 2007. This is an overall increase of 149% with increases ranging from 222% for morphine, 280% for hydrocodone, 319% for hydromorphone, 525% for fentanyl base, 866% for oxycodone, to 1,293% for methadone. Average sales of opioids per person have increased from 74 milligrams in 1997 to 369 milligrams in 2007, a 402% increase. Surveys of nonprescription drug abuse, emergency department visits for prescription controlled drugs, unintentional deaths due to prescription controlled substances, therapeutic use of opioids, and opioid abuse have been steadily rising. This manuscript provides an updated 10-year perspective on therapeutic use, abuse, and nonmedical use of opioids and their consequences.

Maintenance therapy with methadone or buprenorphine-based regimens reduces opioid dependence and associated harms. The perception that methadone is more effective than buprenorphine for maintenance treatment has been based on low buprenorphine doses and excessively slow induction regimens used in early buprenorphine trials. Subsequent studies show that the efficacy of buprenorphine sublingual tablet (Subutex (R)) or buprenorphine/naloxone sublingual tablet (Suboxone (R)) is equivalent to that of methadone when sufficient buprenorphine doses, rapid induction, and flexible dosing are used. Although methadone remains an essential maintenance therapy option, buprenorphine-based regimens increase access to care and provide safer, more appropriate treatment than methadone for some patients.

Copyright 2010, Wiley-Blackwell

Markowitz JD; Francis EM; Gonzales-Nolas C. Managing acute and chronic pain in a substance abuse treatment program for the addicted individual early in recovery: A current controversy. Journal of Psychoactive Drugs 42(2): 193-198, 2010. (42 refs.)

Patients early in recovery from addictive disorders are in a tenuous position and when these individuals are stressed from acute or chronic pain they face even more challenges. Physicians are often conflicted by the desire to help the patient achieve pain control and maintain sobriety. While there have been a handful of studies examining patients in either active addiction with pain or with a more remote history of addiction with pain, there have been very few, if any, that look at treating patients during their addiction recovery process who suffer from pain. This article will examine the issue of whether it is ever appropriate to use opioid pain medications on such patients and, if so, what guidelines can be used to maximize the chances of a good outcome while minimizing the chances of causing a recurrence or exacerbation of addiction.

Objective: This study aims to test whether recent increases in the reported prevalence of opioid-use disorder in the United States occurred across all age groups (period effect), consistently only among younger age groups (age effect), or varied according to year of birth (cohort effects). Method: Joint analysis of data from the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES) and the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), focusing on individuals ages 18-57, grouped by 10-year age intervals. Sample sizes for the present analyses were 30,846 for the NLAES and 31,397 for the NESARC. Prevalence of lifetime and past-year prescription opioid-use disorder resulting from nonmedical use (abuse and dependence) was examined. Results: Within birth cohorts, prevalence of lifetime prescription opioid-use disorder increased during the 10 years between surveys, indicating the importance of age effects. In addition, lifetime and past-year prevalence of prescription opioid-use disorder was higher among more recent birth cohorts as compared with earlier birth cohorts, indicating the importance of cohort effects. Consistent with a period effect, cross-cohort comparisons showed that risk for prescription opioid-use disorder has increased for all individuals regardless of their birth cohort membership from the NLAES to the NESARC survey. Conclusions: Findings suggest that more problems (abuse and dependence) may emerge as prescription opioid users get older and that more recent birth cohorts are at higher risk for prescription opioid problems.

Aims: Injectable opioids were prescribed unsupervised under the 'British System' for heroin dependence. National guidelines (1999 and 2003) confirmed that injectable opioids have a legitimate 'limited clinical place' and should be dispensed daily, with 'mechanisms for supervision'. This study assesses whether national guidelines impacted on prescriptions of injectable opioids. Methods: A 25% random sample of community pharmacists (n = 2473) in England were surveyed by a questionnaire in 2005, with 95% response (n = 2349). Opioid maintenance prescription data for anonymous patients (n = 9620) were compared to the prescription data in 1995 (n = 3721) from a matched survey. Findings: Injectable opioid prescriptions reduced significantly from 10.5% (1995) to 1.8% (2005) of all opioid maintenance prescriptions. Daily doses significantly increased, as did daily dispensing from 28.8% (1995) to 57.8% (2005), whilst weekly dispensing reduced from 39.5% (1995) to 14.5% (2005). In 2005, injectable opioids accounted for 27.2% of private opioid prescriptions, versus 1.5% National Health Service (NHS) prescriptions. Private prescriptions were for larger take-home doses than NHS prescriptions. Regional variation was present. Conclusions: Injectable opioid maintenance treatment for heroin dependence under the unsupervised 'British System' is disappearing, although not extinct. If injectable opioids are prescribed, this is more in line with national guidelines. However, many prescriptions are less than daily instalments.

Aims: To assess if Scottish drug users, their family and friends could be trained in critical incident management and the safe and effective administration of naloxone. The project also sought to monitor whether drug users can manage their own personal take-home naloxone (THN) supply and use it appropriately in an emergency opiate overdose situation. Methods: Twenty-three clients were trained alongside 18 'buddies' and 19 clients were issued with naloxone packs following successful completion of training. Findings: Three overdoses were witnessed by three participant clients during the pilot with two reported 'saves'; pilot training procedure was followed on both occasions. Each reported overdose was validated by police and ambulance service records. Eighty-nine percent (n = 17) were followed up at 2 months; 94% (n = 16) of these claimed to still have their THN; 89% (n = 17) followed up at 6 months; 100% (n = 17) of these claimed to still have their THN. Results: This data suggests that Scottish drug users can be trained to identify and respond to an opiate overdose utilizing basic life support and naloxone administration skills similar to their counterparts from other parts of the world. Moreover these results suggest that a majority of opiate users can responsibly manage their own personal THN supply when trained appropriately.

Kratom (Mitragyna speciosa) has been used for medicinal and recreational purposes. It has reported analgesic, euphoric and antitussive effects via its action as an agonist at opioid receptors. It is illegal in many countries including Thailand, Malaysia, Myanmar, South Korea and Australia; however, it remains legal or uncontrolled in the UK and USA, where it is easily available over the Internet. We describe a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated dependence on kratom with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating and cravings for the substance. A reducing regime of dihydrocodeine and lofexidine proved effective in treating subjective and objective measures of opioid-like withdrawal phenomena, and withdrawal was relatively short and benign. There are only few reports in the literature of supervised detoxification and drug treatment for kratom dependence. Our observations support the idea that kratom dependence syndrome is due to short-acting opioid receptor agonist activity, and suggest that dihydrocodeine and lofexidine are effective in supporting detoxification.

Aims: The transition from prison back into the community is particularly hazardous for drug-using offenders whose tolerance for heroin has been reduced by imprisonment. Studies have indicated an increased risk of drug-related death soon after release from prison, particularly in the first 2 weeks. For precise, up-to-date understanding of these risks, a meta-analysis was conducted on the risk of drug-related death in weeks 1 + 2 and 3 + 4 compared with later 2-week periods in the first 12 weeks after release from prison. Methods: English-language studies were identified that followed up adult prisoners for mortality from time of index release for at least 12 weeks. Six studies from six prison systems met the inclusion criteria and relevant data were extracted independently. Results: These studies contributed a total of 69,093 person-years and 1033 deaths in the first 12 weeks after release, of which 612 were drug-related. A three- to eightfold increased risk of drug-related death was found when comparing weeks 1 + 2 with weeks 3-12, with notable heterogeneity between countries: United Kingdom, 7.5 (95% CI: 5.7-9.9); Australia, 4.0 (95% CI: 3.4-4.8); Washington State, USA, 8.4 (95% CI: 5.0-14.2) and New Mexico State, USA, 3.1 (95% CI: 1.3-7.1). Comparing weeks 3 + 4 with weeks 5-12, the pooled relative risk was: 1.7 (95% CI: 1.3-2.2). Conclusions: These findings confirm that there is an increased risk of drug-related death during the first 2 weeks after release from prison and that the risk remains elevated up to at least the fourth week.

Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs

Merza Z. Chronic use of opioids and the endocrine system. (review). Hormone and Metabolic Research 42(9): 621-626, 2010. (81 refs.)

Opioids are widely used for the management of acute and chronic pain. They are also abused for recreational purposes. Long term use may lead to abnormalities in the endocrine system. The axis mainly affected is the gonadal axis leading to hypogonadism. However adrenal insufficiency and growth hormone deficiency can also occur with evidence that other hormones are affected to a lesser extent. No large randomised controlled trials have been performed; however, evidence from several small studies on heroin addicts and chronic pain patients support the above. Hence it is important to consider hormonal abnormalities in patients on long term opioids and if suspected appropriate assessment would be warranted.

The relationship between postmortem concentrations of morphine and co-detected psychoactive drugs in fatal overdoses is examined. Morphine and other drugs were detected in 161 medicolegal autopsy cases. Subsets of these morphine-positive cases based on drug class were established, including opioids, antidepressants, ethanol, benzodiazepines, and "other." Each subset was split into high or low concentration groups based on median drug concentrations. Morphine concentrations of the [high] and [low] groups were compared, with no significant difference in morphine concentration identified in the opioid, ethanol, or benzodiazepine subsets. The "other" drug class was too heterogeneous for statistical assessment. Morphine concentrations did show a significant direct relationship (p = 0.01) with antidepressants, namely increased concentrations of antidepressant drugs are associated with an increased concentration of morphine. This trend probably remains even after excluding cocaine-positive cases. The unsuspected finding that postmortem concentrations of antidepressants positively correlate with morphine levels may be important in the treatment of depression in drug addicts.

Thomas de Quincey, a British writer of 19th century, suffered insomnia from the age of 17 years. In his famous "Confessions of an English-Opium Eater" (1822), he described a symptomatology that could concord with restless legs syndrome long before he became addicted to opium. In this report, we analyze his clinical description and the circumstances leading to his opium addiction.

Identification of maternal opioid abuse in pregnancy is often difficult to ascertain in the absence of a reliable self-report. We aimed to characterize an at-risk neonatal population for opioid exposures as well as other drugs of abuse and alcohol. From June 2007 to January 2009, 563 neonatal hair and 1318 meconium specimens were assessed for opioids and were positive in 11.4% and 17.0%, respectively. Neonates testing positive for opioids in hair or meconium analysis were also more likely to test positive for other licit and illicit substances (odds ratiohair, 1.75; 95% confidence interval, 1.03-2.97; odds ratiomeconium, 1.61; 95% confidence interval, 1.16-2.22). Specifically, a positive neonatal hair test for opioids also predicted a positive result for oxycodone. In addition, a positive meconium test result for opioids was associated with positive results for cocaine, oxycodone, methadone, benzodiazepines, and fatty acid ethyl esters (alcohol). Finally, there was a significant correlation between maternal and neonatal hair test results for opioids (Spearman rank rho = 0.657, P = 0.03). Understanding the addiction profiles of these women may lead to better clinical and social management and may largely benefit an at-risk population.

Background: Pharmacological therapy has an important place in the management of opioid dependence. Methadone has been the mainstay of therapy but has a number of limitations. Buprenorphine monotherapy is another option, but misuse and diversion can have negative consequences. The opioid receptor antagonist, naloxone, has been added to buprenorphine to create a combination product with a reduced potential for misuse and diversion. Objectives: This study evaluated the use of buprenorphine/naloxone for 24 weeks as a pharmacological management of opioid-dependent patients after therapeutic switch from buprenorphine alone. Methods: Patients (n = 43) received sublingual tablets of buprenorphine/naloxone. The buprenorphine dose was 2-24 mg (mean 16). Patients saw a physician, including an interview using a structured data sheet, and had counselling each week. Assessments were performed at week 2 (period 1), week 6 (period 2), week 16 (period 3) and week 24 (period 4). Laboratory immunoenzymatic testing was performed weekly to detect drugs in the urine. Results: The management of withdrawal symptoms was rated as 'satisfactory' by 67% of patients during period 1 and 91% during period 4. The majority of patients was highly satisfied with therapy and considered that buprenorphine/naloxone provided good control of cravings. Two patients dropped out of therapy, but all others continued to receive buprenorphine throughout the study. Approximately 50% of patients stated that they disliked the sensory properties (taste, colour, odour and feel) of buprenorphine/naloxone. Adverse effects were as would be expected on the basis of the mechanism of action of buprenorphine (i.e. opioid-induced constipation) and for patients undergoing drug withdrawal. Only 2% of patients attempted the intravenous misuse of buprenorphine/naloxone, none of whom experienced any gratifying effects. Conclusions: Opioid-dependent patients maintained on buprenorphine monotherapy can be safely switched to a sublingual buprenorphine/naloxone tablet without any loss of treatment effectiveness. Buprenorphine/naloxone can be administered in an outpatient or primary care setting, and effectively controls cravings and withdrawal symptoms. Patient satisfaction was high, making retention in treatment more likely.

Background and objective: Sublingual buprenorphine [Subutex (R)] is used to treat opioid dependence. However, illicit intravenous (IV) injection of buprenorphine is a widespread problem. This survey investigated the IV misuse of buprenorphine among patients receiving drug replacement therapy at the Drug Addiction Centre in Udine, Italy. Study design: All patients who were receiving treatment with buprenorphine or methadone at the Drug Addiction Centre were invited to fill in a voluntary and anonymous questionnaire consisting of five questions. The questions asked if the patient had ever misused buprenorphine intravenously, when the misuse had occurred, the patient's reasons for misusing buprenorphine, the patient's perception of their experience, and the patient's perception of how widespread IV misuse of buprenorphine is. 307 patients completed the questionnaire, 93 and 214 of whom, respectively, were receiving buprenorphine and methadone. Results: In total, 23.12% of patients admitted an IV misuse of buprenorphine, with a significantly greater prevalence among patients currently receiving buprenorphine (35.48%) than those receiving methadone (17.75%; p < 0.001). Younger patients were also more likely to have misused buprenorphine, and tended to have done so before coming to the Drug Addiction Centre. The most frequent motivation for IV misuse was treatment of heroin addiction or withdrawal symptoms (50.71%), while only 12.67% of patients reported that their motivation was to experience pleasure or euphoria. The majority of patients who had misused buprenorphine intravenously (53.52%) had a negative experience, and methadone recipients were significantly more likely to find the experience negative than buprenorphine recipients (68.42% vs 36.36%; p = 0.007). Almost half of the patients (45.93%) thought that at least 50% of patients had taken buprenorphine by IV injection. Conclusion: The results of our study confirm the widespread IV misuse of buprenorphine. Misuse was most common among patients currently receiving buprenorphine treatment and younger patients. For the majority of patients, the reason for IV misuse was to treat their dependence. We believe that the prevalence of buprenorphine misuse could be reduced by adopting appropriate clinical practices and treating patients with the buprenorphine/naloxone combination rather than buprenorphine alone.

This cross-sectional study of acute psychiatric admissions compared physicians' assessments of recent substance intake and on-site urine testing with comprehensive laboratory drug analyses. The sample comprised 325 consecutive admissions from 2 acute psychiatric wards. Physicians on call were asked to judge if the patient had recently taken benzodiazepines, opiates, alcohol, amphetamines, cannabis, or cocaine. Blood and urine samples were obtained and analyzed with chromatographic laboratory methods for a wide range of substances. A routine on-site urine screening test was performed in 92 of the cases. Physicians' assessments and on-site urine testing were compared with the reference standard of laboratory analyses. The sensitivity of the physician's assessment was highest for amphetamines (76%), followed by benzodiazepines (61%), opiates (57%), cannabis (55%), and cocaine (50%), whereas specificity was greater than 90% for all substances. The sensitivity of the on-site test ranged from 76% for amphetamine to 97% for cannabis, and specificity ranged from 82% for cannabis to 100% for cocaine. The study indicates clinical underdetection of recent substance intake among acute psychiatric admissions. On-site urine testing identified substance use that was not recognized by the physician's initial assessment, although specificity for cannabis and benzodiazepines was low. Chromatographic methods, which offered important supplementary information about substance use, should be considered for the routine screening of acutely admitted psychiatric patients.

To determine the outcome and factors influencing outcome among a cohort of drug users commencing detoxification from opiate use. National cohort study of randomly selected opiate users commencing methadone detoxification treatment in 1999, 2001 and 2003 (n = 327). One quarter 62 (25.6%) of opiate users had a successful detoxification within the 3-month study criteria. Receiving some inpatient treatment as part of detoxification programme resulted in completion by 56.3% drug users compared to outpatient only treatment (21%). The factors independently influencing detoxification are as follows: having some inpatient treatment AOR 5.9 (2.63-13.64) and never having injected AOR 2.25 (1.20-4.25). An additional 31 (9%) opiate users had a detoxification between 3 months and 1 year and 27 (8%) moved into methadone maintenance. This study finds that having some inpatient treatment increases the likelihood of a detoxification within 3 months. Offering a detoxification early in a drug using career pre-injecting drug use should be considered for suitable and motivated patients.

Urine samples of patients from a heroin maintenance program (FIMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced.

Objectives We have used genome-wide association studies to identify variants that are associated with vulnerability to develop heroin addiction. Methods DNA from 325 methadone stabilized, former severe heroin addicts and 250 control individuals were pooled by ethnicity (Caucasian and African-American) and analyzed using the Affymetrix GeneChip Mapping 100K Set. Genome-wide association tests were conducted. Results The strongest association with vulnerability to develop heroin addiction, with experiment-wise significance (P = 0.035), was found in Caucasians with the variant rs10494334, a variant in an unannotated region of the genome (1q23.3). In African Americans, the variant most significantly associated with the heroin addiction vulnerability was rs950302, found in the cytosolic dual specificity phosphatase 27 gene DUSP27 (point-wise P = 0.0079). Furthermore, analysis of the top 500 variants with the most significant associations (point-wise P <= 0.0036) in Caucasians showed that three of these variants are clustered in the regulating synaptic membrane exocytosis protein 2 gene RIMS2. Of the top 500 variants in African-Americans (point-wise P <= 0.0238), three variants are in the cardiomyopathy associated 3 gene CMYA3. Conclusion This study identifies new genes and variants that may increase an individual's vulnerability to develop heroin addiction.

This study aimed to investigate the effect of antivirals ritonavir and lopinavir/ritonavir on the pharmacokinetics and pharmacodynamics of oral oxycodone, a widely used opioid receptor agonist used in the treatment of moderate to severe pain. A randomized crossover study design with three phases at intervals of 4 weeks was conducted in 12 healthy volunteers. Ritonavir 300 mg, lopinavir/ritonavir 400/100 mg, or placebo b.i.d. for 4 days was given to the subjects. On day 3, 10 mg oxycodone hydrochloride was administered orally. Plasma concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were determined for 48 h. Pharmacokinetic parameters were calculated with standard noncompartmental methods. Behavioral effects and experimental cold pain analgesia were assessed for 12 h. ANOVA for repeated measures was used for statistical analysis. Ritonavir and lopinavir/ritonavir increased the area under the plasma concentration-time curve of oral oxycodone by 3.0-fold (range 1.9- to 4.3-fold; P < 0.001) and 2.6-fold (range 1.9- to 3.3-fold; P < 0.001). The mean (+/- SD) elimination half-life increased after ritonavir and lopinavir/ritonavir from 3.6 +/- 0.6 to 5.6 +/- 0.9 h (P < 0.001) and 5.7 +/- 0.9 h (P < 0.001), respectively. Both ritonavir (P < 0.001) and lopinavir/ritonavir (P < 0.05) increased the self-reported drug effect of oxycodone. Ritonavir and lopinavir/ritonavir greatly increase the plasma concentrations of oral oxycodone in healthy volunteers and enhance its effect. When oxycodone is used clinically in patients during ritonavir and lopinavir/ritonavir treatment, reductions in oxycodone dose may be needed to avoid opioid-related adverse effects.

Introduction and Aims. To explore the combined effects of street-level law enforcement and substitution treatment programs on drug-related mortality, taking into account prevalence of heroin use and changes in injecting behaviour. Design and Methods. Time trend analysis using annual police reports and case register data of opioid substitution treatments in Switzerland, 1975-2007. Results. Drug-related mortality increased during times of more intense street-level law enforcement [odds ratio (OR) 1.32, 95% confidence interval (95% CI) 1.15-1.51], and the number of drug-related deaths predicted the number of heroin possession offences 2 years later (r = 0.97, P < 0.001). Substitution treatment had a protective effect on drug-related mortality (OR 0.23, 95% CI 0.18-0.30). Surprisingly, the number of drug-related deaths was substantially biased by an oscillation period of 14 years (OR 1.24, 95% CI 1.17-1.32). Discussion and Conclusions. Our analysis revealed that the amount of police resources allocated to law enforcement was determined rationally, however, on biased grounds and with untoward consequences. Substitution treatment of heroin users reduced drug-related mortality in the long run, but different factors masked its impact for several years. Therefore, the introduction-or the expansion-of opioid substitution treatment programs should not be promoted with the argument of an immediate reduction of drug-related deaths in a country.

Dropout and recidivism from addiction treatment has been found to be associated with individuals' readiness for change. Motivation for treatment among participants entering the North American Opiate Medication Initiative (NAOMI) randomized controlled trial, which compared heroin assisted treatment (HAT) to optimized methadone maintenance treatment (MMT), was assessed. Through multivariate regression, we aimed to determine whether baseline motivational status was predictive of four treatment outcomes: early dropout, 12-month retention, 12-month response to treatment, and time to discontinuation of treatment. Among the 251 out-of-treatment chronic opioid dependent patients recruited in Montreal, Quebec and Vancouver, British Columbia, 52% reported having a high level of motivation for treatment. HAT was statistically significantly more effective than MMT on each of the outcomes assessed. Baseline motivational status did not predict retention or time to discontinuation in either HAT or MMT. However, while patients were retained in HAT regardless of motivational status, motivated patients showed a more favourable response to treatment in terms of decreases in crime and illicit drug use. These results suggest that HAT successfully retains opioid dependent patients who otherwise may not have been attracted into existing treatment options, and may enhance the odds of successful rehabilitation among patients motivated for treatment.

This randomized, controlled study (n = 256) was conducted to compare three interventions designed to promote hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination completion, among clients undergoing methadone maintenance treatment (MMT) in Los Angeles and Santa Monica. The participants were randomized into three groups: Motivational Interviewing-Single Session (MI-Single), Motivational Interviewing-Group (MI-Group), or Nurse-Led Hepatitis Health Promotion (HHP). All three treatment groups received the 3-series HAV/HBV vaccine. The MI sessions were provided by trained therapists, the Nurse-Led HHP sessions were delivered by a research nurse. The main outcome variable of interest was improvement in HBV and HCV knowledge, measured by a 6-item HBV and a 7-item HCV knowledge and attitude tool that was administered at baseline and at 6-month follow-up. The study results showed that there was a significant increase in HBV- and HCV-related knowledge across all three groups (p < 0.0001). There were no significant differences found with respect to knowledge acquisition among the groups. Irrespective of treatment group, gender (P = 0.008), study site (P < 0.0001) and whether a participant was abused as a child (P = 0.017) were all found to be predictors of HCV knowledge improvement; only recruitment site (P < 0.0001) was found to be a predictor of HBV knowledge. The authors concluded that, although MI-Single, MI-Group and Nurse-Led HHP are all effective in promoting HBV and HCV knowledge acquisition among MMT clients, Nurse-Led HHP may be the method of choice for this population as it may be easier to integrate and with additional investigation may prove to be more cost efficient.

Copyright 2010, Springer

O'Connor PG. Advances in the treatment of opioid dependence continued progress and ongoing challenges. (editorial). Journal of The American Medical Association 304(14): 1612-1614, 2010. (15 refs.)

Background: Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Objectives: To assess the effectiveness and safety of using an opiate compared to a sedative or non-pharmacological treatment for treatment of NAS due to withdrawal from opiates. Search strategy: The review was updated in 2010 with additional searches CENTRAL, MEDLINE and EMBASE supplemented by searches of conference abstracts and citation lists of published articles. Selection criteria: Randomized or quasi-randomized controlled trials of opiate treatment in infants with NAS born to mothers with opiate dependence. Data collection and analysis Each author assessed study quality and extracted data independently. Main results: Nine studies enrolling 645 infants met inclusion criteria. There were substantial methodological concerns in all studies comparing an opiate with a sedative. Two small studies comparing different opiates were of good methodology. Opiate (morphine) versus supportive care (one study): A reduction in time to regain birth weight and duration of supportive care and a significant increase in hospital stay was noted. Opiate versus phenobarbitone (four studies): Meta-analysis found no significant difference in treatment failure. One study reported opiate treatment resulted in a significant reduction in treatment failure in infants of mothers using only opiates. One study reported a significant reduction in days treatment and admission to the nursery for infants receiving morphine. One study reported a reduction in seizures, of borderline statistical significance, with the use of opiate. Opiate versus diazepam (two studies): Meta-analysis found a significant reduction in treatment failure with the use of opiate. Different opiates (six studies): there is insufficient data to determine safety or efficacy of any specific opiate compared to another opiate. Authors' conclusions: Opiates compared to supportive care may reduce time to regain birth weight and duration of supportive care but increase duration of hospital stay. When compared to phenobarbitone, opiates may reduce the incidence of seizures but there is no evidence of effect on treatment failure. One study reported a reduction in duration of treatment and nursery admission for infants on morphine. Compared to diazepam, opiates reduce the incidence of treatment failure. A post-hoc analysis generates the hypothesis that initial opiate treatment may be restricted to infants of mothers who used opiates only. In view of the methodologic limitations of the included studies the conclusions of this review should be treated with caution.

Background: Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Treatments used to ameliorate symptoms and reduce morbidity include opiates, sedatives and non-pharmacological treatments. Objectives: To assess the effectiveness and safety of using a sedative compared to a non-opiate control for NAS due to withdrawal from opiates, and to determine which type of sedative is most effective and safe. Search strategy: This update included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2010), MEDLINE 1966 to April 2010 and abstracts of conference proceedings. Selection criteria Trials enrolling infants with NAS born to mothers with an opiate dependence with > 80% follow-up and using random or quasi-random allocation to sedative or control. Control could include another sedative or non-pharmacological treatment. Data collection and analysis Each author assessed study quality and extracted data independently. Main results: Seven studies enrolling 385 patients were included. There were substantial methodological concerns for most studies including the use of quasi-random allocation methods and sizeable, largely unexplained differences in reported numbers allocated to each group. One study reported phenobarbitone compared to supportive care alone did not reduce treatment failure or time to regain birthweight, but resulted in a significant reduction in duration of supportive care (MD -162.1 min/day, 95% CI -249.2, -75.1). Comparing phenobarbitone to diazepam, meta-analysis of two studies found phenobarbitone resulted in a significant reduction in treatment failure Sedatives for opiate withdrawal in newborn infants (Review) 1 typical RR 0.39, 95% CI 0.24, 0.62). Comparing phenobarbitone with chlorpromazine, one study reported no significant difference in treatment failure. In infants treated with an opiate, one study reported addition of clonidine resulted in no significant difference in treatment failure, seizures or mortality. In infants treated with an opiate, one study reported addition of phenobarbitone significantly reduced the proportion of time infants had a high abstinence severity score, duration of hospitalisation and maximal daily dose of opiate. Authors' conclusions: Infants with NAS due to opiate withdrawal should receive initial treatment with an opiate. Where a sedative is used, phenobarbitone should be used in preference to diazepam. In infants treated with an opiate, the addition of phenobarbitone or clonidine may reduce withdrawal severity. Further studies are needed to determine the role of sedatives in infants with NAS due to opiate withdrawal and the safety and efficacy of adding phenobarbitone or clonidine in infants treated with an opiate for NAS.

Background: Medically prescribed diacetylmorphine, the active ingredient of heroin, has been shown to be effective for the treatment of severe opioid addiction. However, there are no data regarding its effectiveness among Aboriginal heroin injectors. Methods: The present analyses were performed using data from the NAOMI study (North American Opiate Maintenance Initiative), an open-label randomized controlled trial that compared the effectiveness of injectable diacetylmorphine (45.8%) and hydromorphone (10%) vs. oral methadone (44.2%) among long-term treatment-refractory opioid-dependent individuals. Rates of retention and response to treatment were analyzed among participants from the Vancouver site (n=192). Results: Baseline profiles were similar among Aboriginal (n=60) and non-Aboriginal (n=132) participants except for higher HIV positive rates among Aboriginal people (23.3% vs. 8.3%). Among Aboriginal participants in the injection and methadone groups, retention rates at 12 months were 84.4% vs. 57.1% and response rates were 68.8% vs. 53.4%, respectively. Aboriginal and non-Aboriginal rates were not significantly different. Discussion: Offering treatment assisted with medically prescribed diacetylmorphine or hydromorphone to long-term treatment-refractory opioid-dependent Aboriginal people could be an effective way to attract them into and retain them in treatment as well as dramatically reduce the risk of HIV infection.

Background: There is consistent evidence showing women access treatment with more severe substance-related profiles relative to men; however, treatment outcome evaluation shows inconclusive results regarding gender differences. Furthermore, few studies evaluate response by gender. Methods: The present analyses were performed using data from the NAOMI study, an open-label, phase Ill randomized controlled trial, carried out between 2005 and 2008 in Vancouver and Montreal, Canada. A total of 226 long-term treatment-refractory opioid dependent individuals were randomized to receive injectable diacetylmorphine or oral methadone for 12 months. Patients in both treatment groups were offered psychosocial and primary care services. Main outcomes were retention in addiction treatment at 12 months. Drug use, health, psychosocial adjustment and health-related quality of life were examined at baseline and during treatment, using the European Addiction Severity Index, Maudsley Addiction Profile, SF-6D and EuroQol EQ-5D. Results: A total of 88 (38.9%) females and 138 (61.1%) males were included in the present analysis. Retention rates among female participants in the diacetylmorphine group were significantly higher than oral methadone (83.3% vs. 47.8%). Males receiving diacetylmorphine improved significantly more than females in physical health, health-related quality of life, and family relations but female participants in the diacetylmorphine group had significantly greater improvements in illicit drug use scores and psychological health compared to females allocated to oral methadone. Conclusions: Among long-term opioid dependent women who have not benefited sufficiently from available treatments, medically prescribed diacetylmorphine is more effective than oral methadone. Men receiving diacetylmorphine showed more improvements than women.

Background: Unstable housing and homelessness is prevalent among injection drug users (IDU). We sought to examine whether accessing addiction treatment was associated with attaining stable housing in a prospective cohort of IDU in Vancouver, Canada. Methods: We used data collected via the Vancouver Injection Drug User Study (VIDUS) between December 2005 and April 2010. Attaining stable housing was defined as two consecutive "stable housing" designations (i.e., living in an apartment or house) during the follow-up period. We assessed exposure to addiction treatment in the interview prior to the attainment of stable housing among participants who were homeless or living in single room occupancy (SRO) hotels at baseline. Bivariate and multivariate associations between the baseline and time-updated characteristics and attaining stable housing were examined using Cox proportional hazard regression models. Principal Findings: Of the 992 IDU eligible for this analysis, 495 (49.9%) reported being homeless, 497 (50.1%) resided in SRO hotels, and 380 (38.3%) were enrolled in addiction treatment at the baseline interview. Only 211 (21.3%) attained stable housing during the follow-up period and of this group, 69 (32.7%) had addiction treatment exposure prior to achieving stable housing. Addiction treatment was inversely associated with attaining stable housing in a multivariate model (adjusted hazard ratio [AHR] = 0.71; 95% CI: 0.52-0.96). Being in a partnered relationship was positively associated with the primary outcome (AHR = 1.39; 95% CI: 1.02-1.88). Receipt of income assistance (AHR = 0.65; 95% CI: 0.44-0.96), daily crack use (AHR = 0.69; 95% CI: 0.51-0.93) and daily heroin use (AHR = 0.63; 95% CI: 0.43-0.92) were negatively associated with attaining stable housing. Conclusions: Exposure to addiction treatment in our study was negatively associated with attaining stable housing and may have represented a marker of instability among this sample of IDU. Efforts to stably house this vulnerable group may be occurring in contexts outside of addiction treatment.

Context. Fentanyl is a powerful opioid used for the induction of anesthesia as well as for the management of severe pain. In recent years, transdermal fentanyl "patches" have become popular for outpatient management of chronic pain. The high potency and outpatient availability of fentanyl has also made it a highly sought-after drug of abuse. Deaths in which fentanyl is detected challenge medical examiners who must decide whether a given case represents therapeutic administration or overdose. Objectives. The current review seeks to present data about fentanyl that are relevant to the interpretation of postmortem blood and tissue fentanyl concentrations as well as to highlight areas which can be helpful or misleading in the evaluation of deaths potentially related to fentanyl exposure. Methods. Standard searching of the PubMed database for studies, case series, and case reports involving fentanyl kinetics, chemistry, and postmortem behavior was performed. Search terms typically included "postmortem" and "fentanyl," as well as "kinetics" and "analysis," where appropriate. Additional references were located as citations from reviewed papers or as conference abstracts. Results and Conclusions. The postmortem behavior of fentanyl is influenced heavily by pH changes and the antemortem kinetic behavior of the drug, especially, by its distribution. Postmortem blood fentanyl concentrations do not correlate directly with antemortem blood concentrations. Without adequate evaluation of kinetic data, investigative information and consideration of postmortem changes, misinterpretation of postmortem fentanyl results is likely.

Objectives: The aim of the study was to identify physical, psychological, and social risk factors associated with opioid medication misuse among community-dwelling older adults with chronic pain. Methods: Using a cross-sectional research design, a confidential survey was administered at 11 outpatient clinics affiliated with the Baltimore Veterans Affairs Medical Center and the University of Maryland Medical System. A sample of 163 older adults (response rate 80.7%) with chronic pain and receiving opioid medications provided demographic information and responded to survey items. Severity of pain, alcohol problems, physical disability, depressive symptoms, spirituality, social support, and social network were assessed. Descriptive statistics and exploratory regression analyses were employed to determine factors independently associated with misuse. Results: Higher levels of pain severity and depressive symptoms, and lower physical disability scores were significantly associated with increased risk of opioid medication misuse. Alcohol problems, spirituality, social support, and social network were not associated with opioid medication misuse. Discussion: High pain intensity scores may indicate undertreatment of pain or may represent a rationalization to justify opioid medication use. Higher levels of depressive symptoms have been noted in the chronic pain population and may contribute to misuse of opioid medications for psychic effects. Less physically disabled persons are more likely to misuse opioid medications or older person receiving multiple medications may wish to avoid potential adverse drug effects. While there was an association between lower levels of disability and higher risk for opioid medication misuse, a causal relationship could not be determined.

Study Design. Case report. Objective. Describe a case of chronic occupational low back pain with various treatments of questionable efficacy, leading to prolonged disability, iatrogenic narcotic addiction, and opioid-induced hyperalgesia. Summary of Background Data. Concerns about narcotics and other questionable treatments for chronic low back pain are increasing, especially in those with work-related conditions. Methods. Medical record review. Results. The patient had significant, persistent low back symptoms, but good function at work and home. He underwent lumbar fusion to address persistent pain, and subsequently developed failed back surgery syndrome. He was prescribed increasing amounts of opioid analgesics and was recommended for an intrathecal morphine pump, without evaluation of the safety or efficacy of his current regimen. Subsequently, he was hospitalized for opioid detoxification and substance abuse treatment. Conclusion. Patients with chronic low back pain are at risk for receiving ineffective and potentially harmful treatment. A focus on restoring function instead of complete pain relief may lead to better outcomes in these patients.

Lifetime potential and probable pathological gambling (PG) were assessed using the South Oaks Gambling Screen (SOGS) questionnaire. The prevalence between patients in methadone maintenance treatment (MMT) in Tel Aviv (Israel, gambling is illegal) and MMT patients in Las Vegas (NV, USA, gambling is legal) was compared. Urine toxicology and substance use was assessed as well. PG at MMT admission was higher in Tel Aviv (48/178, 27%) than in Las Vegas (19/113, 16.8%; p = .05). In Tel Aviv gambling mostly preceded opiate abuse (58.3%), while it followed opiate abuse in Las Vegas (66.7%, p < .001). Only 20.8% in Tel Aviv and 21.1% in Las Vegas were currently gambling. Multivariate analyses found older age on admission to MMT odds ratio (OR) = 1.05 (95% confidence interval [CI] 1.01-1.08), being male OR = 2.6 (95% CI 1.3-5.3) and being from the Tel Aviv MMT clinic OR = 2.5 (95% CI 1.3-4.9) to characterize PG. Detection of any drug in MMT admission urine specimens was unrelated to PG. Older age on admission to MMT, and male gender characterized PG in different MMT clinics, independent of the legal status of gambling. Low current PG rates for patients in both MMT clinics suggest that legality may not be relevant.

The success of high-dose buprenorphine (HDB) as substitution therapy for major opioid dependence is related to its partial agonist effect on opioid receptors, which in theory makes it very safe to use. However, numerous deaths directly attributable to buprenorphine have been described in the literature. These deaths are generally related to misuse of HDB with intravenous administration and/or concomitant use of benzodiazepines, and they usually occur in patients on HDB substitution therapy for opioid dependence. We present three deaths attributed to HDB which arose from uncommon mechanisms and led to unusual forensic situations. The first death was that of a patient admitted to hospital after simultaneous prescription of HDB, clonazepam, oxazepam, and cyamemazine. The second death followed forcible administration of a very low dose of HDB to a patient with post-hepatitis C cirrhosis and heart failure. The third death was subsequent to an HDB overdose, probably with suicidal intent, in a young woman who had not been prescribed the drug as opiate substitute. Such deaths raise the question of the mechanisms involved and draw attention to the resulting unusual forensic situations.

Objective. The aim of this secondary analysis of the South African National HIV Prevalence, Incidence, Behaviour and Communication (SABSSM) 2008 survey is to provide current data on illicit drug use that could assist in the development and implementation of effective substance abuse policies and intervention programmes aimed at these populations in South Africa. Method. A multistage random population sample of 15 828 people age >= 15 (56.3% women) was included in the survey. Illicit drug use was assessed by 2 sections of the Alcohol, Smoking and Substance use Involvement Screening Test (ASSIST). Frequency analyses for different age groups, geolocality, educational level, income, and population group were calculated, as were odds ratios for these variables regarding combined illicit drug use. Results. Current cannabis use was reported by 3.3% of the population sample-6.1% of the men and 1.2% of the women and the use of combined all-other illicit drugs (cocaine, amphetamines, inhalants, sedatives, hallucinogens, opiates) was reported by 1.8% of the participants. Coloured men (14.3%) were most likely, and Indian or Asian women (0.6%) least likely, to be cannabis users. Illicit drug use (combined) among men was associated with the 20 - 34-year age group and the coloured and white population groups, and among women in the younger age groups, the coloured and white population groups, and low and higher income. Conclusion. An increase of cannabis and other illicit drug prevalence rates was observed from 2005 (2.1%) to 2008 (3.3%) in the population sample. Multilevel interventions are required to target illicit drug users, in addition to creating awareness in the general population of the problems associated with illicit drug use. There is a need to address illicit drug use in national and provincial policy planning and intervention efforts and, in terms of treatment, a need to ensure that treatment practitioners are adequately trained to address illicit drug use. Future prospective studies are necessary to assess the impact of illicit drug use.

Remifentanil is a relatively new ultrashort action synthetic opioid. Studies on the use of remifentanil in neonatology have emerged demonstrating its effectiveness and safety in neonates. The present study describes the use of remifentanil in both full-term and premature newborns, highlighting the theoretical benefits for this population in terms of both neonatal intensive care and anaesthesia. A Medline search was undertaken of all reviews and reports about the use of remifentanil in neonates published between 1996 and 2009 using MeSH search terms 'remifentanil', 'analgesia', 'anaesthesia', 'newborn' and 'neonate'. The review points that remifentanil has been used with advantages in newborns including preterm neonates and even for foetal anaesthesia. It proved to be a good option to attenuate the hemodynamic/endocrine markers of stress related to surgery. Owing to its unique pharmacokinetic profile, shorter extubation times can be achieved that makes the drug also a good option for short duration invasive procedures in NICUs (InSurE). A concern on its use is that the hemodynamic response (hypotension) may become significant when the drug is associated to other drugs like sevoflurane. Conclusion: Remifentanil seems to be an effective and safely used opioid for neonatal intensive care and anaesthesia practice.

Background: During 1999-2006, rates of unintentional drug-related deaths increased 120% in the U.S. Purpose: This report describes demographics and trends of unintentional medication overdose deaths among Oklahoma residents to target prevention strategies. Methods: Oklahoma medical examiner data regarding fatal unintentional poisonings involving at least one prescription or over-the-counter medication during 1994-2006 and opioid retail sales data during 1997-2006 were analyzed during 2008-2009 to determine demographic-specific rates of overdose deaths and changes in 3-year mean death rates. Results: A total of 2112 fatal unintentional medication overdoses were identified (4.7 deaths/ 100,000 population) involving a median of two substances/decedent. The highest fatality rates occurred among men (5.9/100,000) and people aged 35-54 years (11/100,000). Crude overdose death rates increased sevenfold during the investigation period, peaking at 11/100,000 in 2006. Death rates increased more for women (ninefold) than men (sixfold); rates among residents of rural counties increased more (eightfold) than urban county rates (sixfold). Leading drug types involved in fatalities were opioids and anxiolytics. The individual drugs contributing most frequently included methadone (31%); hydrocodone (19%); alprazolam (15%); and oxycodone (15%). During 1997-2006, Oklahoma prescription opioid sales increased fourfold. Methadone was associated with the highest number of deaths per equianalgesic dose sold (23.3), whereas hydrocodone and oxycodone had the highest increases in deaths per equianalgesic dose sold (threefold increase each). Conclusions: Unintentional medication-related deaths are increasing in Oklahoma and often involve multiple substances. Substances most frequently contributing to deaths were prescription opioid analgesics. Prevention strategies should target people aged 35-54 years and emphasize the dangers of coingesting substances and misusing prescription pain medications.

To examine the clinical spectrum of complications in pulmonary system and changes of some parameters of humoral and cell mediated immunity related to heroin overdose. The study includes 16 patients who are long-term heroin abusers with acute heroin and mixed with other psychoactive drugs intoxications with an average age of 21,5 +/- 5.04 years (12 men and 4 woman). All patients were hospitalized in the Clinic of Toxicology, MHATEM "N.I.Pirogov", Sofia. We have used clinical, clinico-laboratory, immunological, chimicotoxicological, instrumental methods. In severe intoxications with heroin and other psychoactive drugs, we observed pulmonary system complications, i.e. pneumonia, aspiration of gastric contents, noncardiogenic pulmonary edema (NCPE) and acute respiratory distress syndrome (ARDS.). Of the 16 patients in our study, 3 patients died due to complications. Some changes in the immune reactivity observed in the study were (1) statistically significant lower mean levels of IgG and (2) tendency to lower mean levels of IgA, IgM and complement components - C3 in the studied patients in comparison with the values in healthy people. The changes were more demonstrative in the group with pulmonary complications compared to the group without pulmonary complications. We observed that the CD4 lymphocytes were significantly less in the studied patients; in addition, a lower level of CD56-bearing lymphocytes (natural killer /NK/ cells) was observed in comparison to healthy controls. The results show that the mixture of acute heroin with other psychoactive drugs leads to complications in the pulmonary system and changes of some parameters of cell-mediated and humoral immunity.

Physicians who prescribe opioid analgesics for patients with moderate to severe chronic pain face a balancing act in the wake of the current publicity regarding abuse (nonmedical use) of prescription pain killers. There is a spectrum of opioid abuse ranging from those who misuse the drug by not following doctor's orders to those who take the drugs to achieve a high or divert the drugs to the street market for profit. Formulations of opioid analgesics designed to resist or deter abuse have been proposed, and are now either on the market or in the pipeline. These are innovative formulations that make the drug less convenient or less desirable to abusers. This article examines three such new products along with clinical studies that report on their safety and effectiveness. These drugs include extended-release morphine with sequestered naloxone (Embeda (R)), controlled-release oxycodone in a high-viscosity hard gelatin capsule (Remoxy (R)) and an immediate-release oxycodone tablet with subtherapeutic niacin as an aversive agent (Acurox (R) with niacin tablets). Extended-release morphine with sequestered naltrexone offers a pharmacological barrier in that pellets of morphine surround an internal core of naltrexone (ratio 100 : 4 of morphine : naltrexone), which is released if the tablet is compromised by chewing or crushing. The hard gelatin capsule of controlled-release oxycodone was designed to resist tampering and the drug cannot be extracted with a needle. The immediate-release oxycodone formulation with subtherapeutic niacin uses a gel-forming ingredient designed to inhibit inhalation and prevent extraction of the drug for injection. The subtherapeutic niacin is intended to induce flushing and other unpleasant effects if the drug is taken in an excessive quantity. While these drugs hold individual promise, it remains undetermined if they can truly prevent abuse. Drug-seeking individuals are extremely resourceful and show little loyalty to a particular drug when other drugs are available. It is possible that abuse-deterring formulations may divert such individuals to find other drugs that are easier to compromise. Nevertheless, these formulations are important innovations and warrant further study to assess their appropriate role as analgesics.

Background. The aim of the study was to explore the epidemiology of drug abuse treatment in South Africa. Methods. Treatment demand statistics were analysed from South African National Council on Alcoholism and Drug Dependence and the South African Community Epidemiology Network on Drug Use records, and a rapid situation assessment was conducted. Twenty-one key informant interviews were conducted in all 9 provinces among provincial substance abuse co-ordinators, and one manager per treatment centre from a sample of treatment centres. Three focus groups were conducted and 46 self-administered questionnaires were distributed among inpatients at 2 selected treatment centres in Free State and North West provinces. Qualitative data were analysed using grounded theory, and quantitative data analysed using SPSS. Results. Treatment records show that the most frequent substance of abuse was alcohol (51%), followed by cannabis (21%), crack/cocaine (9.6%), heroin/opiates (7.9%), methamphetamine (Tik) (4.5%), prescription/over-the-counter drugs (2.0%), and cannabis/mandrax (1.7%). More substance abusers were male, of lower education, white or black, than were female, more highly educated, coloured and Indian/Asian. Key informant interviews showed that females are the 'hidden' substance abusers and tend not to be identified in research statistics and at treatment centres. Poverty, unemployment, lack of recreational facilities, being surrounded by substance abusers, and long work shifts were also mentioned as factors contributing to substance abuse. The age of initiation of substance abuse using non-drugs such as glue was 9 years old, alcohol 10 - 12 years old, dagga 11 - 12 years old, poly-drug use (alcohol, tobacco and dagga) 14 years old, and harder drugs such as cocaine and heroin at 16 - 17 years old, as reported by key informants. Family care and support, improved socio-economic conditions and increased law enforcement would help to discourage substance abuse. Conclusion. Prevention interventions and policies in South Africa should focus on reducing substance abuse by targeting the 'at risk populations' identified in this study.

Aim: To assess whether the co-ingestion of opiates in acute paracetamol overdose has an effect on the paracetamol level 4 h after ingestion. Methods: A prospective observational study was performed in the emergency department of a teaching hospital. The paracetamol levels at 4 h of consecutive patients who had taken an overdose of either paracetamol alone or in conjunction with an opiate were collected over a 4-month period. The data were then analysed. Results: After exclusions, the results of 21 patients who took paracetamol alone and 20 who took paracetamol and an opiate showed that paracetamol levels were significantly lower at 4 h if there was co-ingestion of an opiate. Analysis shows that opiate ingestion is a predictor for paracetamol levels at 4 h. Conclusion: Co-ingestion of opiate decreases the serum paracetamol level at 4 h. If opiate and paracetamol are taken together, there is a case for a repeat measurement of the paracetamol level if the level at 4 h is lower than would be expected in selected patients.

This is a reprint of a paper originally published in 1977, in the Proceedings of the Thirty-Ninth Annual Scientific Meeting of the Committee on Problems of Drug Dependence. It is a seminal article based on follow-up of Vietnam Veterans who tested positive for heroin use upon their return from Vietnam. A number of the findings were wholly unexpected, such as the ease of ceasing heroin use without treatment and without signficant problems. The conclusion was that in late 1974 was no more likely to be used regularly or daily if used at all than were marijuana or amphetamines. It was more likely to be used regularly than other narcotics and other non-narcotic drugs. As compared with marijuana and amphetamines, what is distinctive about heroin is not its liability for daily use, but the fact that daily users perceive themselves as dependent. Despite their dependence, they manage to quit use much more often than anyone would have guessed and can often even return to use without becoming dependent again. Heroin users are polydrug users of an extreme kind, who use a greater variety of other drugs than do less regular heroin users. People who use heroin are highly disposed to have serious social problems even before they touch heroin. Heroin probably accounts for some of the problems they have if it is used regularly, but heroin is "worse" than amphetamines or barbiturates only because worse people use it. What are the policy implications of our findings? It would seem that our society has overemphasized the importance of treatment for heroin per se, failing to pay attention to the multiple other problems that heroin addicts have. Heroin addicts are deeply involved with a great variety of other drugs at the same time they are involved with heroin, and they have all kinds of social adjustment difficulties that are not entirely attributable to heroin. It is small wonder that our treatment results have not been more impressive, when they have focused so narrowly on only one part of the problem.

Aims: To analyse whether changes in maintenance treatment of opiate-dependent subjects in Sweden were related to changes in opiate-related mortality and inpatient care from 1998 to 2006. Design: We collected data from surveys of methadone maintenance treatment units, of buprenorphine and methadone sales, and of mortality and inpatient care in Sweden. Setting: Sweden. Participants: Patients in maintenance treatment. Measurements: Survey data of treatment policy to all units in 2003 and 2005. Trend tests and correlation analyses of data on sales, mortality, inpatient care and forensic investigations. Findings: The surveys showed a marked change to a less restrictive policy, with increased use of 'take-away doses' and a reduction of discharges due to side misuse. The one-year retention rate stayed high. Sales of buprenorphine and methadone and the number of patients in treatment increased more than threefold from 2000 to 2006, with the greatest increase for buprenoprphine, introduced in year 2000. There was a significant 20-30% reduction in opiate-related mortality and inpatient care between 2000-2002 and 2004-2006 but not of other drug-related mortality and inpatient care. This decline was larger in Stockholm County, which had a less restricted treatment policy. However, a significant increase in buprenorphine- and methadone-related mortality occurred. For the study period 1998-2006, statistically significant declines occurred only in Stockholm County. Conclusions: The liberalization of Sweden's drug policy correlated with an increase in maintenance treatment, a decrease in opiate-related mortality and inpatient care and an increase in deaths with methadone and buprenorphine in the tissues.

Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs

In order to examine risk factors for attempting suicide in heroin dependent patients, a group of 527 abstinent opiate dependent patients had a psychiatric interview and completed the Childhood Trauma Questionnaire. Patients who had or had never attempted suicide were compared on putative suicide risk factors. It was found that 207 of the 527 heroin abusers (39.3%) had attempted suicide. Attempters were younger; more were female, reported childhood trauma, a family history of suicidal behavior, a history of aggression, treatment with antidepressant medication, and alcohol and cocaine dependence. Logistic regression revealed that a family history of suicidal behavior, alcohol dependence, cocaine dependence, and treatment with antidepressant medication were significant predictors of attempting suicide. These results suggest that attempting suicide is common among opiate dependent patients and that both distal and proximal risk factors may play a role.

Objectives: The objective of the study was to analyse the practice of giving take-home dosages of opioid medications to patients with reference to the reasons for and the quantity of the medications given as additional or extra take-home dosages. Methods: All the patients were checked regarding the kind of medication, urine samples, reasons for extra take-home dosages and their quantity. Results: Of the 150 patients selected for the group in the programme, 27 needed one or more extra take-home dosages in 2007. 10 (11*) of those patients had negative urine samples for all illicit drugs and never used alcohol at any stage of the year of the study. 7 patients used marijuana, benzodiazepines or alcohol only once or just occasionally in that year. 10 patients used other illicit drugs or used alcohol and benzodiazepines more often. Among the reasons for extra take-home dosages, hard physical work was listed 7 times, vomiting because of the bad taste of the medication 3 times, difficulties in intiating medical therapy after entering the programme 3 times, vomiting as a part of illness twice and lowering the dosage too quickly twice. Other reasons were listed once each. Altogether, the percentage of the overall quantity of medications received by patients during the year as extra take-home dosages was: 0.47% for methadone, 0.75% for buprenorphine and 0.10% for SR morphine. Conclusions: Reviewing the fairly good results of treatment at the centre, therapeutic decisions to give additional take-home dosages to the patients have proved to be reasonable and usually correct. Throughout this study a continual therapeutic wish to achieve a better understanding of opioid addiction as just one among other chronic diseases has been made evident.

The aim of study was determine the effect of ultra-rapid opiate detoxification (UROD) on the presence or absence of withdrawal syndrome in a group of patients with opiate dependency. In this study, withdrawal syndrome of 173 patients with opiate addiction was evaluated before and after UROD using the Objective Opioid Withdrawal Scale. Hence, each patient was observed for 5 minutes before UROD and at different hours afterward to observe any withdrawal sign. The most prevalent withdrawal sign before UROD was anxiety. Restlessness was the most prevalent finding at 1, 3, and 6 hours. After 12 hours, yawning was reported as the most prevalent finding in 39 participants. Anxiety was reported as the most prevalent finding in 61 participants after 24 hours. Patients with opioid dependency who underwent UROD showed the highest rate of withdrawal symptoms at one hour after anesthesia. Most of these symptoms subsided after 24 hours. UROD can be applied for detoxification of patients with opioid dependency with safety.

Treatment is effective in reducing heroin use and clinical and social problems among heroin addicts. The effectiveness is related to the duration of treatment. "VEdeTTE" is an Italian longitudinal study funded by the Ministry of Health to evaluate the effectiveness of treatments provided by the National Health Services. The study involved 115 drug treatment centers and 10,454 heroin users. Clinical and personal information were collected at intake through a structured interview. Treatments were recorded using a standardized form. Survival analysis and Cox Proportional Hazard model were used to evaluate treatment retention. Five thousand four hundred and fifty-seven patients who started a treatment in the 18 months of the study were included in the analysis: 43.2% received methadone maintenance therapy (MMT), 10.5% therapeutic community, and 46.3% abstinence-oriented therapy (AOT). The likelihood of remaining in treatment was 0.5 at 179 days. The median daily dose of methadone was 37 mg. Psychotherapy was provided in 7.6% of patients receiving methadone and 4.9% of those in therapeutic community. Type of therapy was the strongest predictor of retention, with AOT showing the lowest retention. In MMT patients, retention improved according to dose. Living alone, psychiatric comorbidity and cocaine use increased the risk of dropout. Psychotherapy associated halved the risk of dropout.

This study investigated association between post-traumatic stress disorder (PTSD) and a 1-year follow-up heroin use among female clients in methadone clinics in Israel. Participants were 104 Israeli female clients from four methadone clinics (Mean age = 39.09, SD = 8.61) who reported victimization to childhood sexual abuse. We tested traces in urine of these female clients for heroin a year preceding and a year following the assessment of their PTSD. Results show that 54.2% reported symptoms that accedes the DSM-IV criteria for PTSD. We found that among childhood victimized women PTSD is associated with more frequent use of heroin at a 1-year follow-up even after controlling for duration of the stay at the clinic, background, other traumatic experiences and heroin use a year prior the assessment of their PTSD. This study shows the potential long-run negative consequences of childhood sexual abuse. Not only are these sexually abused women trapped into drug dependence and addiction, they cannot break the vicious cycle of continuing the use of illicit drugs even when treated for their addiction. One major practice implication is that treatment for PTSD proven efficacious will be provided in the methadone and other drug treatment services.

Objectives: This study examines potential predictors (e.g., attachment style, frequency of therapeutic treatment sessions) of client-rated therapeutic alliance between the social worker and client. The relationship between therapeutic alliance and client's psychological outcomes (hope and posttraumatic stress symptoms [PTS's]) was also assessed. Methods: The study sample included 95 of 193 female clients (average age 39.35, SD 8.66) at four methadone clinics in Israel. Results: Clients reported a strong therapeutic alliance with their social workers. Stepwise hierarchical multiple regression analyses revealed that only the frequency of treatment sessions, the avoidance dimension of attachment, and less frequent opiate use were significant predictors of therapeutic alliance. Therapeutic alliance significantly predicted hope but did not predict reduced PTS. Conclusions: Implications for social work practice and future research are discussed.

Aim: To investigate the difference in fetal heart rate of opioid-dependent mothers compared to non-dependent mothers in the first trimester of pregnancy. Design: The data of 74 consecutive singleton pregnancies of mothers enrolled in a maintenance programme for opioid-dependent women was matched to 74 non-exposed singleton pregnancies by maternal age, crown-rump length, smoking status, ethnic background and mode of conception. Measurement: Fetal heart rate measured as part of first-trimester screening by Doppler ultrasound between 11+0 and 13+6 gestational weeks was compared retrospectively. Findings: The mean fetal heart rate in opioid-dependent mothers was 156.0 beats per minute (standard deviation 7.3) compared to 159.6 (6.5) in controls. The difference in fetal heart rate was significant (P = 0.02). There was a significant difference in mean maternal body mass index (P = 0.01) but not in mean nuchal translucency (P = 0.3), gestational age (0.5), fetal gender (P = 0.3) and parity (P = 0.3) between both groups. Fifty-five per cent (41 of 74) of cases were taking methadone, 30% (22 of 74) buprenorphine and 15% (11 of 74) were taking slow-release morphines throughout the pregnancy. Conclusions: In fetuses of opioid-dependent mothers a decreased fetal heart rate can already be observed between 11+0 and 13+6 gestational weeks. The effect of opioid intake needs to be taken into consideration when interpreting fetal heart rate in opioid-dependent mothers at first-trimester screening.

About one in every three individuals will experience chronic pain in their lifetime, and opioids are known to be an effective means to treat this condition. Much attention, however, has been given to the fact that prescription opioid analgesics are some of the most frequently abused drugs, and misuse is prominent in patients with chronic pain. Several new opioid formulations that are designed to prevent or deter the abuse of opioids are currently in development, and two have been approved for marketing (morphine sulphate co-formulated with naltrexone hydrochloride [Embeda (R)] and a new formulation of the extended-release oxycodone [OxyContin (R)]). In this article, we review the various types of abuse-deterrent and tamper-resistant formulations in clinical development. We believe that continued advances in opioid formulations can help mitigate risk for those with legitimate need for pain control, but only if used rationally in the context of good clinical practice.

Background: Severely opioid-dependent patients are at high risk of both acquiring and spreading the hepatitis C virus (HCV). It is uncertain, however, whether these patients are possible candidates for HCV treatment. We therefore explored treatment retention and adherence as well as sustained viral response in co-morbid severely opioid-dependent subjects under heroin maintenance, who previously failed in conventional substitution treatment or were not in any drug treatment. Methods: All patients in heroin maintenance in the German heroin trial, who received standard antiviral HCV therapy with pegylated interferon and ribavirin, were included. Co-consumption of licit and illicit drugs was tolerated as long as it did not interfere with treatment. Results: Twenty-six patients in heroin maintenance were treated for chronic HCV infection. Both the Global Severity Index of the Symptom Checklist 90-R (average score 65.9) and the Opiate Treatment Index (average score 16.6) indicated relevant co-morbidity. Twenty-one patients (81%) were retained in treatment; the adherence rate was 92%. Eighteen patients (69%) achieved a sustained viral response, with a 100% response rate for genotype 2, 90% for genotype 3, and 42% for genotype 1. Discussion: This is the first study that investigates the feasibility of antiviral HCV treatment in a well-defined sample of co-morbid severely opioid-dependent subjects in heroin maintenance treatment. Viral response rates are comparable to non-drug-user populations. Within a need-adapted treatment setting, HCV treatment may even be extended to difficult-to-treat opioid-dependent patients.

The present study was designed to examine the association of positive youth development with the likelihood of tobacco, alcohol, marijuana, hard drug, and sex initiation between 5th and 10th grades. A national, largely middle-class sample of 5,305 adolescents, participating in a longitudinal study funded by the National 4-H Council (although not all participants were enrolled in 4-H or other after-school programs), completed measures of positive youth development (PYD) constructs and of tobacco, alcohol, marijuana, and hard drug use once per year between 5th and 10th grades. At the 9th and 10th grade assessments, adolescents were asked whether they had initiated sexual intercourse and, if so, at what age they had first engaged in intercourse. Although the present sample was somewhat lower risk compared to national averages, survival analysis models indicated that PYD was significantly and negatively associated with the initiation hazards for tobacco use, marijuana use, and sex initiation for girls only, and with hard drug use for both genders. PYD was also positively associated with the odds of condom use across genders. Results are discussed with regard to PYD as a preventive process.

Objective: To estimate the relationship between maternal methadone dose and the incidence of neonatal abstinence syndrome (NAS). Study design: We performed a retrospective cohort study of pregnant women treated with methadone for opiate addiction who delivered live-born neonates between 1996 and 2006. Four dose groups, on the basis of total daily methadone dose, were compared (<= 80 mg/d, 81-120 mg/d, 121-160 mg/d, and >160 mg/d). The primary outcome was treatment for NAS. Symptoms of NAS were objectively measured with the Finnegan scoring system, and treatment was initiated for a score >24 during the prior 24 hours. Results: A total of 330 women treated with methadone and their 388 offspring were included. Average methadone dose at delivery was 117 +/- 50 mg/d (range, 20-340 mg/d). Overall, 68% of infants were treated for NAS. Of infants exposed to methadone doses <= 80 mg/d, 81-120 mg/d, 121-160 mg/d, and >160 mg/d, treatment for NAS was initiated for 68%, 63%, 70%, and 73% of neonates, respectively (P = .48). The rate of maternal illicit opiate abuse at delivery was 26%, 28%, 19%, and 11%, respectively (P = .04). Conclusion: No correlation was found between maternal methadone dose and rate of NAS. However, higher doses of methadone were associated with decreased illicit opiate abuse at delivery.

This study explored the association between readiness to enter treatment and performance on the Wisconsin Card Sorting Test (WCST), a measure of problem solving ability and executive functioning. Data for this analysis was collected on 258 current regular users of heroin and/or cocaine as part of an epidemiologic study on executive function and drug use. A structural equation model was used to test the hypotheses that poorer performance on the WCST would predict lower scores on two latent constructs measuring motivation to change drug use. Specifically, poorer performance on the WCST was associated with lower recognition of problem use. Associations between treatment enrollment within the past six months and regular use of more than one drug were also observed. Findings highlight the importance of considering cognitive impairment in programs targeting active drug users and promoting treatment participation.

Many opioid-dependent patients do not receive care for addiction issues when hospitalized for other medical problems. Based on 3 years of clinical practice, we report the Transitional Opioid Program (TOP) experience using hospitalization as a "reachable moment" to identify and link opioid-dependent persons to addiction treatment from medical care. A program nurse identified, assessed, and enrolled hospitalized, out-of-treatment opioid-dependent drug users based on their receipt of methadone during hospitalization. At discharge, patients transitioned to an outpatient interim opioid agonist program providing 30-day stabilization followed by 60-day taper. The nurse provided case management emphasizing HIV risk reduction, health education, counseling, and medical follow-up. Treatment outcomes included opioid agonist stabilization then taper or transfer to long-term opioid agonist treatment. From January 2002 to January 2005, 362 unique hospitalized, opioid-dependent drug users were screened; 56% (n = 203) met eligibility criteria and enrolled into the program. Subsequently, 82% (167/203) presented to the program clinic post-hospital discharge; for 59% (119/203) treatment was provided, for 26% (52/203) treatment was not provided, and for 16% (32/203) treatment was not possible (pursuit of TOP objectives precluded by medical problems, psychiatric issues, or incarceration). Program patients adhered to a spectrum of medical recommendations (e.g., obtaining prescription medications, medical follow-up). The Transitional Opioid Program (TOP) identified at-risk hospitalized, out-of-treatment opioid-dependent drug users and, by offering a range of treatment intensity options, engaged a majority into addiction treatment. Hospitalization can be a "reachable moment" to engage and link drug users into addiction treatment.

Substance use during pregnancy is a major public health concern. This study examined differences in substance use among pregnant women from rural and urban areas. Participants were 114 pregnant women entering a hospital-based inpatient detoxification unit primarily for Opiate Dependence who voluntarily agreed to a face-to-face interview. Substance use measures were based on the Addiction Severity Index gathering information about lifetime, past 12 months, and 30 days prior to admission. Rural pregnant women had higher rates of illicit opiate use, illicit sedative/benzodiazepine use, and injection drug use (IDU) in the 30 days prior to admission. Additionally, a greater proportion of rural pregnant women reported the use of multiple illegal/illicit substances in the 30 days prior to entering detoxification. More specifically, pregnant women from rural areas were 8.4 times more likely to report illicit opiate use, 5.9 times more likely to report IDU, 3.3 times more likely to report illicit sedative/benzodiazepine use, and 2.8 times more likely to report the use of multiple illegal/illicit substances in the 30 days prior to entering inpatient detoxification, after adjustment for socio-demographic characteristics (including education and income), pregnancy characteristics, physical and mental health indicators, and criminal justice system involvement. The increased rates of prescription opiate and benzodiazepine use as well as IDU among rural pregnant women are concerning. In order to begin to understand the elevated rates of substance abuse among rural pregnant women, substance use must be considered within the context of demographic, geographic, social, and economic conditions of the region.

Copyright 2010, Wiley-Blackwell

Shaw C. The effectiveness of an innovative model of community opiate detoxification provided on a supported one-to-one basis. Journal of Substance Use 15(5): 340-351, 2010. (30 refs.)

Aim: To evaluate the effectiveness of an innovative model of community opiate detoxification provided on a supported one-to-one basis. Method: Analysis of data collected from participants who entered the detoxification programme during the pilot phase (March 2008-January 2009) is presented. Following an initial pre-detoxification interview each participant was subsequently interviewed at the end of detoxification and 1-month post-detoxification. Face-to-face structured interviews were conducted at each stage, which included items relating to drug use, drug withdrawal, desires for drugs, anxiety, depression, and arousal; and qualitative questions relating to participant's opinions regarding the detoxification programme. Results: Seventeen participants were admitted (15 males, mean age 39.2). Eleven participants (64.7%) exited the detoxification unit drug free. Non-significant decreases in drug use were observed amongst participants who completed follow-up. There was a significant reduction in participant's severity of withdrawal symptoms, but no difference in desires for drugs, depression, anxiety, or arousal. Participants felt positive about their detoxification experience and that the one-to-one model had contributed to detoxification success. Conclusions: This paper highlights the potential of a one-to-one model of opiate detoxification as an alternative to either the well established, home-based detoxification or the inpatient model. This study demonstrates its viability, initial level of effectiveness and positive participant perceptions, highlighting the requirement for further exploration of novel approaches to drug treatment.

There is a paucity of research on pharmacotherapies in adolescents with substance use disorders. This paucity is partly because of the fact that most people with substance dependence do not get diagnosed until early adulthood, that is, after 18 years of age. This article reviews pharmacotherapies used for aversion, substitution, anti-craving, and detoxification of alcohol, nicotine, cocaine, and opioids dependence. Adult research is referenced when applicable and generalized to adolescents with caution. Continued evaluation and development of pharmacotherapy for youth in controlled studies are needed to examine medication effectiveness, safety, potential for abuse, compliance, and potential interactions with other medications or substances of abuse.

Internet forums record the opinions and advice exchanged about pregnancy under Subutex. Two hundred and fourteen messages under 92 nicknames from four forums, especially dedicated to this subject in France, from August 2005 to July 2008 were collected and analyzed with QSR NIVIVO8. Most of the Internet users were women, pregnant, or with children, using Subutex. Very few professionals took part in them. The analysis of the opinions and representations of this substance, of medical practices, of exchanged advice, particularly on posology, was realized by the construction of a thematic tree.

Objective. To evaluate the effect of the use of benzodiazepines on prescription of opioids 4-7 years later in patients with noncancer pain. Design. A cohort of 7,991 men and 9,083 women aged 40, 45 and 60 years who reported no use of opioids in health surveys in 2000-2001 was linked to the nationwide Norwegian Prescription Database, and their prescriptions of opioids during 2004-2007 were analyzed. Moderate-high prescription frequency of opioids was defined as at least 12 prescriptions during the period January 2004-December 2007. Results. The unadjusted odds ratio for moderate-high prescription frequency of opioids for individuals who had previously used benzodiazepines was 7.7 (95% confidence interval 5.6-10.5) as compared with previous nonusers. After adjustment for musculoskeletal pain, alcohol, smoking habits, and socioeconomic variables, the odds ratio was lowered to 3.1 (2.1-4.6). The analysis of the effect of benzodiazepines and chronic pain individually and in combination suggest that use of benzodiazepines is an even stronger predictor of later opioid use than self-reported chronic pain. Conclusions. Our study suggests that earlier use of benzodiazepines may predict repeated use of opioids. Before starting pain treatment with opioids, clinicians should take into consideration the possibility of substance abuse and mental health disorders. A central issue when prescribing opioids for chronic noncancer pain is to balance the risk of problematic use of these drugs with the benefits of pain relief.

Background: Although early trauma is a well-recognized risk factor for both dissociation and substance abuse, there are inconsistent reports on the association between substance abuse and dissociation. This inconsistency may be resolved by the "chemical dissociation" hypothesis that suggests that some substance abuse patients may not exhibit high levels of dissociation, despite their trauma history, because they may achieve dissociative-like states through chemicals consumption. This article describes 2 studies aimed to (a) assess the incidence of dissociative psychopathology among recovering opioid use disorder (OUD) patients and (b) examine the chemical dissociation hypothesis. Methods: One hundred forty-nine patients receiving treatment in a heroin recovery program and 46 controls were administered self-report measures of dissociation and childhood maltreatment in study I. A similar battery and an assessment of addiction severity were completed by 50 methadone maintenance treatment (MMT) patients and 30 detoxified OUD patients in study 2. In addition, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Dissociative Disorders Revised was administered to a subsample of MMT and detoxified OUD patients. Results: Patients with OUD reported higher levels of child maltreatment and dissociation than controls. Although MMT and detoxified patients did not differ in severity of addiction and child maltreatment, detoxified outpatients had higher levels of dissociation than MMT outpatients: 23% of the detoxified patients and 12% of the MMT patients were diagnosed with a dissociative disorder. Conclusions: These findings support the chemical dissociation hypothesis of OUD and suggest that detoxification programs should take into consideration the high incidence of comorbid dissociative disorders among their recovering OUD patients.

In the oncology community, opioids recently have become the cornerstone of cancer pain management. This has led to a rapid increase in opioid prescribing in an effort to address the growing public health problem of chronic pain. A new paradigm in noncancer pain management has emerged, that of risk assessment and stratification in opioid therapy. Techniques foreign to cancer pain management have now become commonplace in the noncancer pain setting, such as the use of monitoring compliance via urine drug screens. Amidst these strides in opioid use for pain management, cancer has been changing. The survival rate has increased, and a group of these patients with chronic pain were treated with opioid therapy. With opioid exposure being longer and against the backdrop of prescription drug abuse, the question is how much of the adaptation of the risk management paradigm in chronic pain management is to be imported to cancer pain management?

The interpretation of toxicological findings is critical for the thorough investigation of the use and abuse of psychoactive substances. A positive analytical result for a sample taken could usually result in criminal proceedings and a punitive outcome for the defendant whose sample was analysed. The detection of markers of illicit opiate misuse is important both in the management of substance misuse and in the postmortem identification of illicit opiate use. The aim of this study was to emphasise the role of opiate biomarkers available at the laboratory and in the clinical environment. Urine remains the biological tool of choice for qualitative detection of illicit drug use in a clinical setting, while quantitative accuracy remains strictly the domain of blood. Accurate interpretation of the screening tests within a clinical setting alongside other relevant information remains the key to the usefulness of any test. Moreover, the finding of a morphine/codeine concentration ratio in blood exceeding unity is a strong evidence that the person had used heroin, as opposed to having taken a prescription analgesic drug containing codeine.

Our goal was to determine whether treatment of depressive symptoms with escitalopram during buprenorphine treatment for opioid dependence would improve treatment retention compared to placebo in a 12-week, randomized, double-blind trial. Treatment dropout was defined as missing seven consecutive buprenorphine dosing days. Participants were 76% male, 80% non-Hispanic Caucasian, and 64% heroin users. At baseline, the mean Beck Depression Inventory II (BDI-II) score was 28.4 (+/- 9.7). Sixty-one percent of participants completed the 12-week buprenorphine protocol. Dropout rates were 33.3% and 44.0% among those randomized to escitalopram or placebo, respectively (p = .19). Relative to baseline, mean BDI-II scores were significantly lower at all follow-up assessments, but the Treatment x Time interaction effect was not statistically significant (p = .18). Participants randomized to escitalopram also did not have a significantly lower likelihood of testing positive for either opiates or other drugs during follow-up. Depressive symptoms often resolved with buprenorphine treatment, and the immediate initiation of escitalopram does not improve treatment retention, depression outcomes, or illicit drug use. Clinicians should determine the need for antidepressant treatment later in buprenorphine care.

Copyright 2010, Elsevier Science

Sternfeld I; Perras N; Culross PL. Development of a coroner-based surveillance system for drug-related deaths in Los Angeles County. Journal of Urban Health. Bulletin Of the New York Academy Of Medicine 87(4): 656-669, 2010. (46 refs.)

Existing data sources do not provide comprehensive and timely information to adequately monitor drug-related mortality in Los Angeles County. To fill this gap, a surveillance system using coroner data was developed to examine patterns in drug-related deaths. The coroner provided data on all injury deaths in Los Angeles County. A list of keywords that indicate a death was caused by drug use was developed. The cause of death variables in the coroner data were searched for mentions of one of the keywords; if a keyword was detected, that death was classified as drug related. The effectiveness of the keyword list in classifying drug-related deaths was evaluated by matching records in the coroner death data to records in the state death files. Then, the drug-related deaths identified using the keywords were compared to drug-related deaths in the state mortality files identified using International Classification of Death codes. Toxicological test results were used to categorize drug-related deaths based on the type and legality of the drug(s) ingested. Mortality rates were calculated for each category of drug and legal status and for different demographic groups. Compared to the gold standard state mortality files, the coroner data had a sensitivity of 95.6% for identifying drug-related deaths. Over three quarters of all drug-related deaths tested positive for opiates and/or stimulants. Males, Whites, and 35-54-year-olds each accounted for more than half of all drug-related deaths. The surveillance of drug-related deaths using coroner data has several advantages: data are available in a timely fashion, the data include information about the specific substances each victim ingested, and the data can be broken down to compare mortality among specific subpopulations.

This article presents the case of a 3 year old patient found shivering and unattended outside a large shopping mall. She was transferred to a large urban hospital emergency room, was slipping in and out of consciousness. A physical exam found multiple bruises abrasions. A bolus of Narcan (naloxone) was administered. Later an immunoassay indicated the presence of opiates. This subsequently proved to be false positive. The authors note that (1) Immunoassays used to screen for the presence of drugs of abuse may not be specific for the intended drug or class and may cross-react with other prescription and nonprescription drugs. (2) Confirmatory testing with a second method with greater analytical specificity and lower detection limits is useful when a screening result is questioned or needs to be verified. Confirmatory testing is commonly required in legally sensitive cases. (3) Both screening and confirmatory tests use cutoff concentrations to distinguish between positive and negative results. The results of drug or drug metabolite tests may be truly negative, or the drugs or their metabolites may be present at concentrations below the cutoff value used and thus be reported as negative or not detected. and (4) Drugs and drug metabolites that share structural similarities with the target compound may cross-react with the antibodies used in screening immunoassays.. Cross-reactivity experiments may be useful in confirming conflicting clinical results. It is noted that when interpreting toxicology results, clinicians and laboratory scientists should remember that pediatric patients have a different pharmacokinetic profile than adults for many substances.

Information concerning acute myocardial infarction after heroin usage is limited and the actual mechanism of heroin-induced myocardial infarction is not well known. Only one report has been described noting the association between usage heroin and acute myocardial infarction in a young man with normal coronary arteries. We also reported a patient with normal coronary arteries and acute myocardial infarction after heroin abuse.

Urine toxicology screening testing is an important standard of care in the addiction and pain treatment setting, offering a reproducible, unbiased, and accurate laboratory test to monitor patients and provide objective support for clinical observations. It has been shown that physicians do not have proficiency in the ordering or interpretation of these tests. This article is an attempt to respond to that need. Current antibody-based enzymatic immunoassays (EIAs) used for urine toxicology screening are useful to detect classes of drugs (ex., opiate) but cannot determine which specific drug (ex., morphine) is present. Gas chromatography and mass spectroscopy can determine exactly which drugs are present, allowing prescribed (or illicit) opiates and benzodiazepines to be identified. This article will discuss principles and details of opiate and benzodiazepine EIA and gas chromatography and mass spectroscopy urine toxicology testing. The approach to detecting patients attributing positive opiate EIAs to prescription opiates who are using heroin or other opioids will be reviewed. Cases of controlled prescription drugs that do not produce the expected positive urine tests (ex., oxycodone producing negative opiate screening tests) will be discussed. How to differentiate codeine from heroin and the role of poppy seeds in toxicology will be examined. The case of an anti-depressant drug that produces false-positive benzodiazepine results and antibiotics that cause positive opiate urine toxicology results will be reviewed. Common benzodiazepines (ex., clonazepam and lorazepam) that do not reliably produce positive benzodiazepine EIAs will be discussed. The approach to detection and management of all these types of toxicology cases will be reviewed, and it is hoped that the analyses presented will impart an adequate information base to medical providers and staff members of drug treatment and pain centers, enabling them to order and interpret these tests in the clinic more effectively as an integrated part of whole patient care.

Objective: To describe trends in the regional and demographic characteristics of injection drug use (IDU) during pregnancy. Methods: Data were obtained from the Treatment Episode Data Set (TEDS), an administrative data set that captures admissions to federally funded treatment centers in the United States. Demographic and treatment-related measures were examined and compared between injection drug and noninjection drug admissions. The results were stratified by year of admission to assess trends over time. Results: From 1994 to 2006, there were 239,511 admissions of pregnant women, of whom 34,717 (14.4%) reported IDU. There was little change in the proportion of injecting from year to year. Compared with admissions of noninjecting pregnant women, a greater proportion of injection drug users were white (68.5 vs. 48.6%), reported heroin use (70.0% vs. 13.2%), and had no health insurance (48.2% vs. 40.2%). Over the time period, the proportion of injection drug users was seen to spread from the West to the South and Northeast for heroin and to the Midwest for amphetamines. Conclusions: IDU among pregnant women in drug treatment remains a significant public health issue, especially among white women.

A comprehensive study of various psychoactive substances and their metabolites was performed in the wastewater treatment plant of the city of Zagreb (780 000 inhabitants) using liquid chromatography/tandem mass spectrometry (LC-MS-MS). The estimation of drug abuse for five different illicit drugs, including heroin, cocaine, marijuana, amphetamine and ecstasy, was made on the basis of their representative excretion rates, which were determined over a period of 8 months. Marijuana (1000 kg/year), heroin (75 kg/year) and cocaine (47 kg/year) were found to be the most frequently consumed illicit drugs, while the consumption of amphetamine-type drugs was much lower (1-3 kg/year). A comparison with other reports indicated that drug abuse profiles in transition countries might be different from those reported for Western Europe, in particular with respect to the comparatively increased consumption of heroin. Enhanced consumption of stimulating drugs (cocaine and ectasy) was systematically detected during weekends.

Objective: To determine if a relationship exists between the dose of heroin and/or substitute medication used in pregnancy and neonatal abstinence syndrome (NAS). Data Sources: Ovid online was used to search the following: EMBASE, Ovid MEDLINE, CINHAL, PscyINFO, Cochrane Database of Systematic Reviews. Study Selection: English language journal articles reporting original research undertaken and published between 1995 and 2009 that examined relationships between NAS and opiate use in pregnancy and with patterns of substance abuse that reflect those of the United Kingdom and other high-resource settings. Data Extraction: The studies were reviewed independently by two authors using predefined quality criteria. Data Synthesis: This was a narrative review; key messages from included studies were discussed in the context of the diversity and commonality of findings in relation to NAS. Conclusions: No correlation between the amount of fetal opioid exposure and expression of NAS was reported in eight of the 10 studies. This observation was consistent across international boundaries, and studies that included both methadone and buprenorphine.

Objectives: Illicit drug use peaks during late adolescence and young adulthood. Turkey has a young population, and, as an historical opium producing country, it has experienced a continual illicit drug abuse problem. This study aimed to estimate the prevalence of substance abuse, to determine the risk factors associated with drug abuse, and to compare the drug abuse between a metropolitan and a rural area. Methods: This was a cross-sectional study performed between March 2007 and May 2008 at 2 universities; 1 from a rural area (Gaziosmanpasa University) and 1 from a metropolitan area (Istanbul University). Results: We found that the most common drugs were minor tranquilizers (5.7%), followed by inhalants (4.9%), and cannabis (3.6%). Cannabis and inhalant abuse were especially common among males. The major risk factors were contact with a person, such as a family member or a peer, who practiced substance abuse, a low level of success at school, being arrested or in trouble with the police, and burglary or theft. Conclusions: These risk factors were similar those identified in developed countries. Similar risk factors were shared between different substances. Hence, preventive measures should target substance abuse in general, rather than focusing on controlling the abuse of individual substances.

Pain is an integral part of the defense mechanisms required for survival. Several hereditary syndromes of complete or almost complete insensitivity to pain have been identified and include channelopathy-associated pain insensitivity, of which the most likely candidate gene is the a-subunit of the voltage-gated sodium channel known as Na(v)1.7. Five hereditary sensory and autonomic neuropathy syndromes have been described. Variable pain sensitivity in the general population has been linked to common variants of the mu-opioid receptor and of the catecholamine-O-methyltransferase genes potentially leading to increased opioid tonus. Variants of the guanosine triphosphate cyclohydrolase 1/dopa-responsive dystonia gene appear to regulate nociception. Other candidate genes are the transient receptor potential cation channel, subfamily 5 member 1, gene and the melanocortin-1 receptor gene. Candidate genes for predicting opioid efficacy are drug-metabolizing enzymes and transporters-including cytochrome P450, uridine 5'-diphosphate-glucuronosyltransferases, and adenosine triphosphate-binding cassette transporters-that are involved in opioid metabolism. Most current knowledge on the genetic regulation of pain has been derived from animal models developed mainly in mice. Genomics has the potential to contribute to therapeutic advances with the promising approach of using small interfering RNA in the control of neuropathic pain. Knowledge of the genetic factors that affect opioid efficacy, metabolism, and adverse effects has the potential for personalizing both acute and chronic pain management, and for designing more useful opiate pain medications with lower adverse event profiles.

Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits that involve several neurotransmitters. One of the neurochemical systems that plays a pivotal role in different aspects of addiction is the endogenous opioid system (EOS). Opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within these reward circuits. Chronic exposure to the different prototypical drugs of abuse, including opioids, alcohol, nicotine, psychostimulants and cannabinoids has been reported to produce significant alterations within the EOS, which seem to play an important role in the development of the addictive process. In this review, we will describe the adaptive changes produced by different drugs of abuse on the EOS, and the current knowledge about the contribution of each component of this neurobiological system to their addictive properties.

Objective. Women represent the largest percentage of new HIV infections globally. Yet, no large-scale studies have examined the experience of pain and its treatment in women living with HIV. Design. This study used structural equation modeling to examine sex differences in pain and the use and misuse of prescription analgesics in a representative sample of HIV+ persons in the United Stated within a prospective, longitudinal design. Outcome Measures. Bodily pain subscale of the Short-Form 36 and Modified Short Form of the World Health Organization's Composite International Diagnostic Interview (opioid misuse). Results. Women reported more pain than men over a roughly 6-month period regardless of mode of HIV transmission or prior drug use history. Men acknowledged more misuse of prescription analgesics over an approximate 1-year period compared with women, after taking into account pain, use of analgesics specifically for pain, and drug use history. Weaker associations between pain and use of analgesics specifically for pain that persisted over time were found among women compared with men. For both men and women, pain was stable over time. Problem drug use history exerted significant direct and indirect effects on pain, opioid misuse, and pain-specific analgesic use across sex. Conclusion. The current findings are consistent with prior evidence indicating female pain predominance as well as the undertreatment of pain among women with HIV. Efforts should be made to improve the assessment and long-term management of pain in HIV+ persons.

Background: Buprenorphine maintenance is efficacious for treating opioid dependence, but problems with diversion and misuse of buprenorphine (BUP) may limit its acceptability and dissemination. The buprenorphine/naloxone combination tablet (BNX) was developed to reduce potential problems with diversion and abuse. This paper provides data regarding the characteristics of BUP injection drug users in Malaysia and preliminary data regarding the impact of withdrawing BUP and introducing BNX. BUP was introduced in 2002 and subsequently withdrawn from the Malaysian market in 2006. BNX was introduced in 2007. Methods: A two wave survey of BUP IDUs was conducted shortly prior to BUP withdrawal from the Malaysian market (n = 276) and six months after BNX was introduced (n = 204). Six focus groups with BUP and/or BNX IDUs were also conducted shortly before the second wave. Results: In addition to current BUP or BNX IOU, 96% of first wave participants and 97% second wave participants reported lifetime heroin IDU preceding the onset of their BUP/BNX IDU. Additionally, 58% of first and 64% of second wave survey participants reported current heroin IDU. Benzodiazepine abuse, often injected with BUP, was reported in both the surveys. Focus group participants reported that BNX was not as desirable as BUP, nonetheless, the results of the second wave survey suggest a continuing widespread BNX IDU, at least in Kuala Lumpur. Conclusions: In Malaysia, BUP and BNX IDU occur among heroin IDUs. The introduction of BNX and withdrawal of BUP may have helped to reduce, but did not eliminate the problems with diversion and abuse.

Background: Ketum (krathom) has been mentioned in the literature as a traditional alternative to manage drug withdrawal symptoms though there are no studies indicating its widespread use for this purpose. This study examines the reasons for ketum consumption in the northern areas of peninsular Malaysia where it is widely used. Methods: A cross-sectional survey of 136 active users was conducted in the northern states of Kedah and Penang in Malaysia. On-site urine screening was done for other substance use. Findings: Ketum users were relatively older (mean 38.7 years) than the larger substance using group. Nearly 77% (104 subjects) had previous drug use history, whilst urine screening confirmed 62 subjects were also using other substances. Longer-term users (use >2 years) had higher odds of being married, of consuming more than the average three glasses of ketum a day and reporting better appetite. Short-term users had higher odds of having ever used heroin, testing positive for heroin and of using ketum to reduce addiction to other drugs. Both groups used ketum to reduce their intake of more expensive opiates, to manage withdrawal symptoms and because it was cheaper than heroin. These findings differ from those in neighbouring Thailand where ketum was used primarily to increase physical endurance. Conclusions: No previous study has shown the use of ketum to manage opioid withdrawal symptoms except for a single case reported in the US. Ketum was described as affordable, easily available and having no serious side effects despite prolonged use. It also permitted self-treatment that avoids stigmatisation as a drug dependent. The claims of so many subjects on the benefits of ketum merits serious scientific investigation. If prolonged use is safe, the potential for widening the scope and reach of substitution therapy and lowering its cost are tremendous, particularly in developing countries.

Background: Woman who struggle with drug addiction during pregnancy are perhaps the most vulnerable of new mothers. The opioid substitution medications methadone and buprenorphine are both compatible with breastfeeding. The objective of this study is to determine breastfeeding rates among opioid-dependent women giving birth in a baby-friendly hospital. Methods: We performed a retrospective chart review of all infants born at Boston Medical Center (Boston, MA) between July 2003 and January 2009 with a diagnosis of neonatal abstinence syndrome. Feeding information was obtained, as well as baseline medical information about the mother-infant pairs. Breastfeeding eligibility was determined by a negative urine toxicology screen on admission, no illicit drug use in the third trimester, and a negative human immunodeficiency virus status. Results: Two hundred seventy-six mother-infant pairs were identified. Forty percent of the mothers carried one or more psychiatric diagnoses; 24% were taking two or more psychiatric medications. Sixty-eight percent of the mothers were eligible to breastfeed; of those, 24% breastfed to some extent during their infant's hospitalization. Sixty-percent of those who initiated stopped breastfeeding after an average of 5.88 days (SD 6.51). Conclusions: Breastfeeding rates among opioid-dependent women were low, with three-quarters of those eligible electing not to breastfeed. Of the minority of women who did choose to breastfeed, more than half stopped within 1 week.

Opioid receptors are critical therapeutic targets for medications development relevant to the treatment of drug dependence and pain. With recent advances in molecular neurobiology, it has become evident that the functional activity of opioid receptors, as ligand-regulated protein complexes, is modulated by multifarious intracellular and extracellular events, that there is genetic variation in coding for receptors, and that the activity of endogenous opioid systems may underlie actions common to other addictive disorders. This supplemental issue of Drug and Alcohol Dependence, arising from an invited symposium at the 71st Annual Meeting of the College on Problems of Drug Dependence, provides a series of contemporary reviews focused on recent advances in opioid neuropharmacology. Each speaker provides herein an invited comprehensive review of the state of knowledge on a specific topic in opioid neuropharmacology. Evans and colleagues describe the multi-faceted control of the opioid G-protein coupled receptor as a dynamic "sensor" complex and identify novel targets for drug development. von Zastrow focuses on opioid receptor-mediated events regulated by endocytosis and membrane trafficking through the endocytic pathway and differential responses to opioid agonists. Blendy and colleague provide a review of human association studies on the functional relevance of the mu opioid receptor variant, A118G. and presents data from the A112G knock-in model, an analogous mouse variant to A118G. Finally, Maldonado and colleagues provide a broader systems review from genetic, pharmacologic and behavioral studies implicating the endogenous opioid systems as a substrate for the mediation of substance use disorders spanning pharmacological classes.

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies.

Behaviors associated with opioid dependence often involve criminal activity, which can lead to incarceration. The impact of a history of incarceration on outcomes in primary care office-based buprenorphine/naloxone is not known. The purpose of this study is to determine whether having a history of incarceration affects response to primary care office-based buprenorphine/naloxone treatment. In this post hoc secondary analysis of a randomized clinical trial, we compared demographic, clinical characteristics, and treatment outcomes among 166 participants receiving primary care office-based buprenorphine/naloxone treatment stratifying on history of incarceration. Participants with a history of incarceration have similar treatment outcomes with primary care office-based buprenorphine/naloxone than those without a history of incarceration (consecutive weeks of opioid-negative urine samples, 6.2 vs. 5.9, p = 0.43; treatment retention, 38% vs. 46%, p = 0.28). Prior history of incarceration does not appear to impact primary care office-based treatment of opioid dependence with buprenorphine/naloxone. Community health care providers can be reassured that initiating buprenorphine/naloxone in opioid dependent individuals with a history of incarceration will have similar outcomes as those without this history.

Two strategies should greatly improve pain management while minimizing opioid abuse. The first strategy involves the systematic implementation in every clinical practice of "universal precautions," a set of procedures that help physicians implement opioid therapy in a safe and controlled manner. These procedures include: 1) carefully assessing the patient's risk for opioid abuse; 2) selecting the most appropriate opioid therapy; 3) regularly monitoring the patient to evaluate the efficacy and tolerability of the treatment and to detect possible aberrant behaviors; and 4) mapping out solutions if abuse and/or addiction is detected, or in case of treatment failure. The second strategy involves the use of opioid formulations designed to deter or prevent product tampering and abuse. Results of clinical trials of new formulations of existing opioids (including oxycodone, morphine, and hydromorphone) suggest the potential for reduced abuse liability and, if approved, will be evaluated after launch for reduced real-world abuse. Integration of these formulations in clinical practices based on universal precautions should help further minimize the risk of opioid abuse while fostering appropriate prescribing to patients with indications for opioid therapy. Perspective: Undertreated pain and prescription opioid abuse remain important public health problems. In the absence of strong empirical evidence, common sense dictates that a universal-precautions approach-a systematic and easily adopted process that clinicians can quickly put into practice-is advised to promote safe opioid prescribing. Abuse-and tamper-resistant opioid formulations are emerging tools that may enhance safe opioid prescribing; further research and postmarketing analysis will clarify their utility and role in clinical practice.

Compelling clinical evidence establishes that buprenorphine is similar to methadone in efficacy for opiate detoxification and maintenance but safer than methadone in an overdose situation. The Drug Abuse Treatment Act of 2000 (DATA 2000) enabled US physicians with additional training to prescribe buprenorphine to a limited number of opiate-dependent patients. The sublingual tablets Subutex (R) (buprenorphine alone) and Suboxone (R) (a combination of buprenorphine and naloxone) meet the specifications of DATA 2000. Suboxone is intended to discourage intravenously administration and has less abuse potential than buprenorphine alone. Suboxone is generally recommended for maintenance treatment except for women who are pregnant. Subutex is recommended in treatment of pregnant women. A buprenorphine opiate withdrawal syndrome can occur in newborns. Although intravenous buprenorphine abuse is a significant public health problem in some countries, buprenorphine alone or in combination with naloxone has less potential for abuse than heroin and some prescription opiates, such as oxycodone. Pharmacotherapy from physicians' offices makes buprenorphine treatment acceptable to some opiate-dependent patients who would not accept treatment in traditional opiate-maintenance clinics. For reasons not adequately understood, some patients find discontinuation of buprenorphine following long-term use difficult. This article reviews the pharmacology of buprenorphine, summarizes evidence supporting the safety and efficacy of buprenorphine and provides clinical guidelines for treatment.

The extent to which interim methadone (IM) without counseling reduces HIV risk behavior has not been reported. The AIDS Risk Assessment scale was administered at baseline and 4-month follow-up to 319 adult heroin-dependent participants randomly assigned to IM or waiting list. On an intent-to-treat basis, there was a significantly greater reduction in drug injection and unprotected sex while high from baseline to follow-up, favoring the IM condition. Remedying the shortage of methadone capacity through the expansion of IM would be a worthwhile approach to reducing the spread of HIV infection.

We review evidence for effectiveness, cost-effectiveness, and coverage of antiretroviral therapy (ART) for injecting drug users (IDUs) infected with HIV, with particular attention to low-income and middle-income countries. In these countries, nearly half (47%) of all IDUs infected with HIV are in five nations-China, Vietnam, Russia, Ukraine, and Malaysia. In all five countries, IDU access to ART is disproportionately low, and systemic and structural obstacles restrict treatment access. IDUs are 67% of cumulative HIV cases in these countries, but only 25% of those receiving ART Integration of ART with opioid substitution and tuberculosis treatment, increased peer engagement in treatment delivery, and reform of harmful policies -- including police use of drug-user registries, detention of drug users in centres offering no evidence-based treatment, and imprisonment for possession of drugs for personal usea -- are needed to improve ART coverage of IDUs.

Health and psychosocial service needs that may be co-morbid with opioid addiction may impede the success of drug treatment among patients attending methadone maintenance treatment programs (MMTPs). This longitudinal panel study investigates whether receipt of services from one or more helping professionals outside of the MMTP confers a benefit for drug treatment outcomes among a random sample of male MMTP patients (N = 356). Each participant was interviewed 3 times, with 6 months between each interview. Since this observational study did not employ random assignment, propensity score matching was employed to strengthen causal validity of effect estimates. Results support hypotheses that receiving additional off-site services has significant beneficial effects in increasing the likelihood of abstaining from cocaine, heroin, and any illicit drug use over both the ensuing 6- and 12-month time periods. These findings indicate that receipt of additional medical and/or psychosocial services enhances the efficacy of methadone treatment in increasing abstinence from illicit drug use.

Objective: To describe malicious administration of pharmaceutical agents to children. Study design: We performed a retrospective study of all pharmaceutical exposures involving children < 7 years old reported to the US National Poison Data System from 2000 to 2008 for which the reason for exposure was coded as "malicious.'' Results: A total of 1439 cases met inclusion criteria. The mean number of cases per year was 160 (range, 124 to 189) that showed an increase over time. The median (IQR) age was 2 (1.5) years. Outcome data were available for 1244 (86.4%) patients. Of these exposures, 172 resulted in moderate or major outcomes or death. 9.7% of cases involved > 1 exposed substance. The most common reported major pharmaceutical categories were analgesics, stimulants/street drugs, sedatives/hypnotics/antipsychotics, cough and cold preparations, and ethanol. In 51% of cases there was an exposure to at least one sedating agent. There were 18 (1.2%) deaths. Of these, 17 (94%) were exposed to sedating agents, including antihistamines (8 cases) and opioids (8 cases). Conclusions: Malicious administration of pharmaceuticals should be considered an important form of child abuse.

Background: Nonmedical prescription opioid use has emerged as a major public health concern in recent years, particularly in rural Appalachia. Little is known about the routes of administration (ROA) involved in nonmedical prescription opioid use among rural and urban drug users. The purpose of this study was to describe rural-urban differences in ROA for nonmedical prescription opioid use. Methods: A purposive sample of 212 prescription drug users was recruited from a rural Appalachian county (n = 101) and a major metropolitan area (n = 111) in Kentucky. Consenting participants were given an interviewer-administered questionnaire examining sociodemographics, psychiatric disorders, and self-reported nonmedical use and ROA (swallowing, snorting, injecting) for the following prescription drugs: buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, OxyContin (R) and other oxycodone. Results: Among urban participants, swallowing was the most common ROA, contrasting sharply with substance-specific variation in ROA among rural participants. Among rural participants, snorting was the most frequent ROA for hydrocodone, methadone, OxyContin (R), and oxycodone, while injection was most common for hydromorphone and morphine. In age-, gender-, and race-adjusted analyses, rural participants had significantly higher odds of snorting hydrocodone, OxyContin (R), and oxycodone than urban participants. Urban participants had significantly higher odds of swallowing hydrocodone and oxycodone than did rural participants. Notably, among rural participants, 67% of hydromorphone users and 63% of morphine users had injected the drugs. Conclusions: Alternative ROA are common among rural drug users. This finding has implications for rural substance abuse treatment and harm reduction, in which interventions should incorporate methods to prevent and reduce route-specific health complications of drug use.

There has been a growing recognition of chronic pain that may be experienced by patients. There has been a movement toward treating these patients aggressively with pharmacologic and nonpharmacologic modalities. Opioids have been a significant component of the treatment of acute pain, with their increasing use in cases of chronic pain, albeit with some controversy. In addition to analgesia, opioids have many accompanying adverse effects, particularly with regard to stability of breathing during sleep. This article reviews the existing literature on the effects of opioids on sleep, particularly sleep-disordered breathing.

Addiction to opiates and illicit use of psychostimulants is a chronic, relapsing brain disease that, if left untreated, can cause major medical, social, and economic problems. This article reviews recent progress in studies of association of gene variants with vulnerability to develop opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems. In addition, we provide the first evidence of a cis-acting polymorphism and a functional haplotype in the PDYN gene, of significantly higher DNA methylation rate of the OPRMI gene in the lymphocytes of heroin addicts, and significant differences in genotype frequencies of three single-nucleotide polymorphisms of the P-glycoprotein gene (ABCBI) between "higher" and "lower" methadone doses in methadone-maintained patients. In genomewide and multigene association studies, we found association of several new genes and new variants of known genes with heroin addiction. Finally, we describe the development and application of a novel technique: molecular haplotyping for studies in genetics of drug addiction.

Accidental opium intoxication in children is an extremely dangerous poisoning if it remains undiagnosed and untreated. The classic triad of miosis, decreased level of consciousness and bradypnea, which are the hallmarks of opiate intoxication, are used for the diagnosis of opium poisoning in adults and children. Little attention has been paid to the signs of opium intoxication in children and no published study has explored the frequency of hallmarks of this type of poisoning in the paediatric population. We conducted a study in order to evaluate the prevalence of major signs of opium poisoning in infants and toddlers. In this study, a total of 228 infants and 82 toddlers who had been admitted to Loghman Hakim Hospital as a result of opium poisoning between 2001 and 2009 were evaluated, retrospectively. The most usual sign of opium poisoning was miosis (90%) followed by a decreased level of consciousness (88.4%), bradypnea (28.4%) and seizure (10.3%). The prevalence of the triad of miosis, bradypnea and a decreased level of consciousness was 25.2%. Miosis in association with decreased level of consciousness was detected in 82.6% of our patients. Bradypnea was present in 74 infants and 14 toddlers, which shows a statistically significant difference (P = 0.01). The mean age and weight of the patients with bradypnea were significantly less than those without bradypnea (P = 0.008 and P = 0.0001, respectively). Bradypnea and seizure were significantly more common in females (36.7% versus 26%; P = 0.05 and 15.2% versus 6.5%; P = 0.01, respectively). Miosis in association with a decreased level of consciousness is the most useful indicator of opium poisoning in infants and toddlers. Furthermore, seizure is a more common feature of this type of poisoning in infants, especially in those who are less than 1 month old.

Several studies on opiates demonstrated that selected brain areas as cerebellum and limbic system have the greatest density of opioid receptors. Recently, few cases of severe cerebellitis following methadone poisoning have been reported in children. We present the case of a 30-month-old girl who developed a delayed encephalopathy after methadone intoxication. She was admitted to our emergency department in coma, and after naloxone infusion, she completely recovered. Five days after intoxication, she developed psychomotor agitation, slurred speech, abnormal movements, and ataxia despite a negative neuroimaging finding. A repeat magnetic resonance imaging (MRI) performed 19 days after the intoxication for persistent symptoms showed signal abnormalities in the temporomesial regions, basal ganglia, and substantia nigra. To our knowledge, this is the first report of these delayed MRI findings associated with synthetic opioid intoxication.

Stress exposure in addicted individuals is known to provoke drug craving, presumably through a memory-like process, but less is known about the effects of stress on non-drug-related affective memory retrieval per se in such individuals, which is likely to provide important insights into therapy for relapse. In present study, we explored the effect of stress on retrieval of neutral and emotionally valenced (positive and negative) words in abstinent heroin addicts. In present study, 28 male inpatient abstinent heroin addicts and 20 sex-, age-, education- and economic status-matched healthy control participants were assessed for 24 h delayed recall of valenced and neutral word lists on two occasions 4 weeks apart once in a nonstress control condition, once after exposure to the Trier Social Stress Test in a counterbalanced design. In addition, attention, working memory, blood pressure, heart rate and salivary cortisol were assessed. We found acute stress at the time of word list recall enhanced retrieval of positively valenced words, but no effect on negative and neutral word retrieval in abstinent heroin addicts was observed. No changes were detected for attention and working memory. The stressor induced a significant increase in salivary free cortisol, blood pressure and heart rate. Stress can enhance non-drug-related positive memory in abstinent heroin addicts. Our findings will provide richer information in understanding dysregulation of their emotional memory processing under stress and hopefully provide insight into designing improved treatments for drug addiction.